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1. Introduction

With the increase in the burden of non-communicable diseases, as well as the growing antimicrobial-resistant infections, the need for new agents that can supply amended therapeutic outcomes has taken on the utmost primacy. Therefore, the investigation of microbes is one of the auspicious ways of finding out lead molecules for drug discovery. Fungi are among the microbes that possess enormous negative and positive influences on human lives [1,2]. They serve as a depository of biometabolites that represent the backbone of different available pharmaceuticals. Moreover, fascinating, structurally unique metabolites, with considerable therapeutic significance as antibiotics as well as anticancer, antidiabetic, antiviral, and immuno-suppressive agents, have been reported in these untapped micro-organisms [3,4,5,6,7,8,9,10,11,12,13]. In addition, they have proved to be superbly efficient decomposers and have developed the capacity to feed on and break down polymeric substances and organic matter by secreting various enzymes, providing sustainable solutions for diverse industries and markets [7,14,15].

Additionally, fungal biotechnology may assist human society’s transition from a petroleum-dependent to a bio-based circular economy. Moreover, they are able to sustainably produce feed, food, chemicals, textiles, fuels, and more [1,2]. On the other hand, they also manufacture toxins that spoil different foods, and they predominantly infect immuno-compromised patients, which drives up public health costs [1,2].

The Aspergillus genus (Trichocomaceae, class Discellaceae), with more than 400 species, represents one of the most prolific genera of filamentous fungi [16]. Aspergillus is an anamorphic (asexual) genus; some of its species have teleomorphs (sexual states), such as A. nidulans, which in its sexual state is called Emericella nidulans [17]. Its species are encountered in outdoor and indoor environments and have relevant medical, food, and industrial applications [16,17,18,19]. Additionally, this genus is renowned for its biosynthesizing of diverse classes of metabolites with myriad bioactivities [5,16,20,21]. Moreover, some of its species have potential biotechnological and industrial applications [16,22]. On the other hand, some cause diverse illnesses to animals and humans [23,24].

Among this species, Aspergillus nidulans Winter G was reported to cause cerebral aspergillosis and is a common pathogen in patients with chronic granulomatous disease [25,26,27]. A. nidulans is well known for its plentiful sources of bioactive metabolites with abundant structural diversity, including terpenoids, alkaloids, polyketides, many of which display various biological activities, such as antioxidant, antialgal, anti-mycobacterial, antiviral, plant growth promoting, cytotoxicity, anti-inflammatory, and antimicrobial activities. In addition, A. nidulans has the potential to secrete various enzymes: laccase, β-glucosidase, keratinase, cellulase, xylanase, lipase, β-galactosidase, cutinase, protease, tannase, and aryl alcohol oxidase [28]. It is noteworthy that the A. nidulans genetic model has been extensively studied regarding cellular development, metabolism, and gene regulation, contributing to an understanding of eukaryotic cell biology and molecular processes, where the capabilities of its genetic manipulation and combining of genetic traits via sexual crossing are important for its marked function as a genetic model [29].

The prime aim of this work is to focus on the stated research on A. nidulans collected from various sources, particularly the structures, biosynthesis, and bioactivities of its metabolites. Moreover, recent reports on its biotechnological relevance, as well as nanoparticle synthesis, have been reviewed. Reported studies from 1953 to November 2022 are presented. The molecular formulae and weights, chemical classes, hosts, location, and bioactivities for its metabolites are listed. The structures of these metabolites according to their chemical classes are summarized. The present work could provide a guide for future expected research exploring the untapped potential of A. nidulans as one of the prosperous producers of bio-metabolites.

2. Methodology

2.1. Data Collection

A survey of the literature was done using assorted databases and publishers: Scopus, PubMed, GoogleScholar, ScienceDirect, Wiley, Taylor & Francis, Bentham, Thieme, MDPI, and Springer. The search was carried out using “Aspergillus nidulans + compounds”, OR “Aspergillus nidulans + NMR”, OR “Aspergillus nidulans + biosynthesis”, OR “Aspergillus nidulans + Biological activity”, “Aspergillus nidulans + Biotechnology”, “Aspergillus nidulans + Enzymes”, OR “Aspergillus nidulans + nanoparticles” as keywords. All chemical structures were drawn utilizing ChemDraw.

2.2. Data Selection

The criteria for the reported data selection included in this review were: (1) studies that reported A. nidulans’ metabolites, including their structures, biosynthesis, and bioactivities, as well as biotechnological importance and nanoparticle synthesis using A. nidulans; (2) all the reported data published in peer-reviewed journals (e.g., articles, reviews, abstracts); and (3) reviews and book chapters. Included studies were assessed through reading of titles, abstracts, and full texts. For non-English articles, the data were extracted from the English abstracts. In this work, published data covering the period from 1953 to November 2022 have been included. In the current work, 103 references have been cited, including various articles and books.

3. Metabolites of Aspergillus nidulans and their Bioactivities

Several studies reported the separation and characterization of assorted classes of metabolites, employing various chromatographic and spectral tools that are surveyed herein, along with their estimated bioactivities and postulated biosynthesis pathways. It was noted that among the diverse metabolites reported from this species, a limited number of them have been assessed for biological capacity (Table 1).

3.1. Benzophenones

A. nidulans and its teleomorph Emericella nidulans are known to biosynthesize prenylated structurally related benzophenones [43,44,45]. Many investigations remarked upon the separation of arugosins, which are interesting fungal metabolites that involve the biosynthesis of structurally related polyketides (e.g., anthraquinones, anthrones, xanthones) (Table 2) [31,43,44,45,46].

The fungus E. nidulans var. acristata, isolated from a Mediterranean green alga, yielded two new benzophenones, arugosins G (10) and H (3), together with arugosins A (7) and B (8) that were separated from the EtOAc extract by Sephadex LH-20/HPLC (Figure 1). These metabolites featured prenyl moieties that are connected to the skeleton via an ether linkage. Compound 3 had antifungal and antialgal potential (IZDs 2 and 3 mm, respectively) vs. Mycotypha microspora and Chlorella fusca, respectively, whereas 7 and 8 (mixture) revealed antibacterial influence vs. Bacillus megaterium (IZD 4 mm) in the agar diffusion assay [43]. Additionally, 7 and 8 demonstrated modest antitumor effectiveness vs. individual cancer cell lines [43]. It is noteworthy that arugosins A (7) and B (8), dibenz[b,e]oxepin metabolites that were formerly reported from A. silvaticus, A. rugulosus, and A. variecolor, and arugosins C and F were obtained from Aspergillus spp. and Ascodesmis sphaerospora, respectively [43].

Arugosin H (3) was proposed as originating from chrysophanol (29, anthrone), which performs oxidative cleavage to produce the aldehyde group, which subsequently undergoes hydroxylation and C-prenylation (Scheme 1). Further, the aldehyde group is converted to a hemiacetal function to produce tricyclic and prenylated metabolites 7, 8, and 10 [43].

3.2. Xanthones and Quinones

Xanthones are dibenzo-γ-pyrone derivatives that differ in the substituents on the benzene rings, relying on modification reactions and biosynthetic origins. Fungal xanthones are polyketides created mainly from acetate units and commonly contain a CH₃ group. It was reported that A. nidulans produces prenylated xanthones with varied structures.

Compounds 14, 16, and 18 are xanthones reported from green alga-derived E. nidulans var. acristata (Table 3). Among them, 18 had antifungal and antialgal capacity (IZDs 11 and 5 mm, respectively) vs. M. microspora and C. fusca. However, none of them exhibited immune-stimulatory potential against cytokine induction in PBMCs [43]. Compounds 14 and 18 were reported from A. nidulans and isolated from Red Sea brown alga, Turbinaria elatensis, using SiO₂ and Sephadex LH-20 CC. They had mild inhibition capacity on HCV NS3/4A protease (IC₅₀s 48.5 and 50.0 μg/mL, respectively), compared to HCV-12 (IC₅₀ 1.5 μg/mL) [47]. In 2018, isosecosterigmatocystin (15), a new xanthone, in addition to 18, was separated and identified from the EtOAc culture extract of A. nidulans MA-143 under 0.1% ethanol stress. Compound 15 was assigned as having 2′S/3′S based on X-ray analysis [30].

The cytotoxic capacity of 18 and 20 vs. NCI-H460, MCF-7, and HeLa cell lines in the SRB was assessed. Only 18 (IC₅₀ 50 μM/mL) possessed growth inhibition capacity vs. the MCF-7 cell, whereas 20 was inactive (IC₅₀ > 100) [53] (Figure 2).

Also, the xanthones were proposed to be biosynthesized from 29, which is transformed by quinone ring oxidative cleavage into thiolester I. Its oxidoreductase-catalyzed reduction yields benzophenone alcohol (II). The alcohol (II) produces 1-hydroxy-6-methyl-8- hydroxymethylxanthone (III) via H₂O elimination, and then hydroxylation via monooxygenase produces 1,7-dihydroxy-6-methyl-8-hydroxymethylxanthone (IV). The latter’s prenyltransferase-catalyzed prenylation results in 12, which is C-prenylated to form 14. Subsequent cyclization of 14 produces 16 and 17 (Scheme 2) [45].

Nidurufin (42), a new metabolite of which is hydroxyaverufin, and 39 were purified from the CHCl₃:MeOH extract of A. nidulans G-106 using silica and formamide-impregnated cellulose powder and characterized by spectral and chemical methods (Figure 3) [51].

The aggregation of the microtubule-accompanied protein tau is substantial in various neurodegenerative illnesses, such as Alzheimer’s disease. Interestingly, 25 and 30 demonstrated potent tau aggregation inhibition potential, which was observed in a filter trap assay and by electron microscopy. In addition, 25 and 30 lessened tau aggregation without blocking tau stabilization of microtubules, like 23.

Together, these metabolites demonstrated potential as lead compounds for developing tau aggregation inhibitors in Alzheimer’s disease and neurodegenerative tauopathies [54]. Isoversicolorin C (36), a new anthraquinone derivative, and six related metabolites—34, 35, 39, 45, and 44—were purified and characterized from the EtOAC culture extract of mangrove-derived A. nidulans MA-143 under ethanol 0.1% stress (Figure 4). Their isolation and elucidation were accomplished by SiO₂/RP-18/Sephadex LH-20 and NMR/ECD/X-ray. Compound 36 had potent antibacterial capacity vs. E. ictaluri and V. alginolyticus (MICs 4.0 and 1.0 μg/mL, respectively); however, 35 possessed capacity vs. M. luteus, E. coli, V. parahaemolyticus, V. alginolyticus, and E. ictaluri (MICs ranged from 1.0 to 8.0 μg/mL), which were comparable to chloramphenicol [30].

3.3. Depsidones and Biphenyl Ethers

Depsidones consist of two 2,4-dihydroxy-benzoic acid moieties, connecting via ester and ether bonds, resulting in 11H-dibenzo[b,e] [1,4] dioxepin-11-one core formation [59]. They originated from depsides’ direct-oxidative coupling of the A 2OH ring and the B 5′ carbon ring. These metabolites were found to have diversified potential: anti-malarial, herbicidal, anti-leishmanial, larvicidal, antifungal, cholinesterase and aromatase inhibitory, and antioxidant activity [59].

Compounds 48 and 49 were separated from the A. nidulans mycelia’s light petroleum ether extract by repeated crystallization from the EtOH and petroleum ether (Table 4). Compound 48 is a monomethyl ether that completely suppressed Mycobacterium tuberculosis growth for 4 weeks, as well as Microsporum audouini and Trichophyton tonsurans, and was inactive against bacteriophages [60].

The co-culture of A. nidulans and A. fumigatus enhanced the production of diphenyl ethers, 52–55, which were separated by SiO₂ CC/HPLC and identified by NMR tools (Figure 5). These metabolites (52–55) possessed antibacterial potential against B. subtilis (MICs 6.3–100 μg/mL) compared to chloramphenicol, indicating that the hydroxylation enhanced the antibacterial effect of diphenyl ethers [32]. In addition, 56 revealed potent antimicrobial effectiveness (MICs 2–4 μg/mL) vs. E. ictarda, A. hydrophilia, E. tarda, and V. harveyi (aquatic pathogens) and C. gloeosporioides (pathogenic plant fungus), which could be further studied in terms of developing antimicrobial agents [31].

3.4. Alkaloids

3.4.1. Quinolone Alkaloids

Natural quinoline alkaloids are an abundant class of alkaloids that have been reported as having animal, plant, and microbial origins. Some investigations remarked upon the separation of quinoline alkaloids from A. nidulans.

A combined analytical and genomic approach and metabolic investigation of A. nidulans HKI 0410 under various culture conditions resulted in aspoquinolones A-D (61–64), which were separated utilizing SiO₂/Sephadex LH-20/HPLC and assigned by NMR [62]. Compounds 61 and 62 are isomers with 3-methoxy-4,6-dihydroxy-4-(4′-methoxyphenyl)quinolinone and unusual 2,2,4-trimethyl-3-oxa-bicyclo[3.1.0]hexane moieties; however, 63 and 64 are diastereomers (ratio 2:1) sharing the same 3-methoxy-4,6-dihydroxy-4-(4′-methoxyphenyl)quinolinone skeleton as 61 and 62 (Figure 6; Table 5). Compounds 61 and 62 exhibited remarkable cytotoxic and antiproliferative capacity on L-929 (GI₅₀ 10.6/11.4 μg/mL) and K-562 (GI₅₀ 17.8/21.2 μg/mL) cell lines, respectively.

These metabolites were postulated as originating from cyclopenin (benzodiazepine, I) formed from anthranilic acid and tyrosine/or phenylalanine, which is biosynthesized by anthranilate synthase (Scheme 3). This enzyme catalyzed the conversion of chorismate to anthranilic acid for tryptophan biosynthesis [62].

From Annelida Whitmania pigra-associated A. nidulansi, aspoquinolones E (65) and F (66), new prenylated quinolinone alkaloids were purified utilizing SiO₂/Sephadex LH-20/HPLC. Their configurations and structures were determined based on spectral and ECD analyses. They featured 3S/4S configuration, with an unusual 2,2,4-trimethyl-3oxa-bicyclo[3.1.0]hexane moiety. Their cytotoxic evaluation vs. A-549, HL-60, and MCF-7 revealed that 65 exhibited moderate cytotoxic capacity (IC₅₀s 3.50, 29.15, and 24.5 μM, respectively) compared to cis-platin (IC₅₀s 13.17, 3.22, and 22.96 μM, respectively). It is noteworthy that 65 and 66, with the same structure but different cyclopropyl ring configuration, were greatly varied in activity, suggesting that the cyclopropyl ring configuration influenced the activity [33].

In 2013, the separation of new 4-phenyl-3,4-dihydroquinolone derivatives, 67–72, along with known related analog 73, was reported from a Rhizophora stylosa-associated A. nidulans MA-143 extract by SiO₂/RP-18/sephadex LH-20/HPLC. Their structures and absolute configuration were established by spectral, ECD, and X-ray analyses. Compounds 70–72 share with 67–69 the 4-phenyl-3,4-dihyroquinolone moiety but lack the terpenoid side chain, as in 67–69. Additionally, 67 was related to 73; however, 67 lacks the cyclohexane moiety in the terpenoid side chain of 73; instead, it features a terminal double bond and substituted tetrahydrofuran moiety. These metabolites did not have cytotoxic (vs. BEL-7402, MDA-MB-231, HL-60, and K562) or antibacterial (E. coli and S. aureus) potential in the MTT and well diffusion methods, respectively, while 68, 69, and 73 had a marked brine shrimp lethality (LD₅₀ 7.1, 4.5, and 5.5 μM, respectively) that was more powerful than colchicine (LD₅₀ 88.4 μΜ) [34].

3.4.2. Quinazolinone, Pyrazine, and Dioxopiperazine Alkaloids

Additionally, four new quinazolinone alkaloids, namely aniquinazolines A–D (74–77), were also purified from E. nidulans using SiO₂/Sephadex LH-20/HPLC and elucidated by spectral analyses, and their absolute configurations were assigned based on acidic hydrolysate chiral HPLC, ECD, and X-ray analyses (Figure 7). Their configurations are 3R/14R/17R/18R/20S (74 and 76), 3R/14R/17R/18R (75), and 14R/17S/18S/20S (77). Compounds 74–77 had potent brine shrimp lethality (LD₅₀s 1.27–4.95 μΜ) compared to colchicine (LD₅₀ 88.4 μΜ). Unfortunately, they did not have anticancer potential vs. MDA-MB-231, BEL-7402, K562, and HL-60 or antibacterial capacity vs. E. coli and S. aureus in the MTT and well diffusion assays, respectively [35].

Emestrin (82), a six-membered-ring dioxopiperazine with a disulfide bridge, is part of the epipoly-thio-dioxopiperazine family obtained from ascidian Aplidium longithorax-associated E. nidulans MFW39 and collected from Wakatobi Marine National Park, Indonesia utilizing SiO₂ CC/HPLC (Table 6). It was found to have noticeable cytotoxic potential (IC₅₀s ranged from 1.8 to 13.8 µg/mL) vs. C28, T47D, HeLa, and HepG₂ but was weakly active against Vero cells (IC₅₀ 260.9 μg/mL). Emestrin (Conc. 1.0 μg/mL) caused G₀/G₁ arrest of the cell cycle, and also induced apoptosis (Conc. 1.0 and 3.0 μg/mL) of 83.6 and 92.6%, respectively, on T47D cells. This effect was linked to a disulphide bond and unique epithio-dioxopiperazine moiety [36]. Another epipolythiodioxopiperazine derivative, emestrin B (83), was separated from marine-derived E. nidulans using SiO₂ CC/preparative TLC and was assessed for cytotoxic capacity in the MTT assay vs. the WiDr, HeLa, and T47D cancer cell lines. It had remarkable cytotoxic influence on IC₅₀s 1.02, 1.56, and 0.16 μg/mL, respectively. This metabolite had apoptotic action against T47D cells (74.1%), compared to doxorubicin (74.8%) [37]. Compound 84, purified from the Nyctanthes arbor-tristis-inhabited fungus strain, had no cytotoxic effectiveness vs. the NCI-H460, MCF-7, and HeLa cell lines in the SRB [53]. Glulisine A (81), a new nitrogenous metabolite, was reported from 1% ethanol-stressed A. nidulans MA-143. It was assigned by NMR and X-ray analyses as being derived from leucine and glutamine [30].

3.4.3. Indole Derivatives

The indole alkaloid emindole DA (97), separated from green alga-associated fungus, possessed antitumor potential vs. 36 human tumor cell line panels (mean IC₅₀s 5.5 µg/mL) in the propidium iodide fluorescence assay [43]. In an antimicrobial assay vs. various aquatic, plant, and human pathogens, terrequinone A (92) exhibited marked efficacy (MIC 2 μg/mL) vs. E. coli, V. alginolyticus, and C. gloeosporioides, compared to chloramphenicol and amphotericin B, suggesting the potency of 92 as a lead metabolite for antimicrobial agents [31]. Ergotryptamine (87) is an alkaloid produced by an engineered A. nidulans WFC that was designated using labeling, MS, and NMR tools. It differs from N-methyl-4-dimethylallyltryptophan (88) by the addition of the OH group, loss of the COOH group, and shifting of the double bond position [64] (Figure 8).

3.4.4. Isoindole Derivatives

The production of new isoindole alkaloids, aspernidine A (99) and B (100 X2), by A. nidulans AXB4A2 cultivated in malt medium at increased orbital shaking (200 rpm) and elevated temperature (37 °C) with p-aminobenzoate/uridine supplementation, was reported. These metabolites were separated via SiO₂/Sephadex LH-20/HPLC and characterized by MS and NMR tools (Figure 9). Compounds 99 and 100 had moderate anti-proliferation potential with respect to L-929 and K-562 (GI₅₀ 35.8/34.3 μM for 99 and 39.5/39.5 μM for 100, respectively) and weak cytotoxicity with respect to HeLa (CC₅₀ 94.0 and 65.5 μM, respectively) [65] (Table 7).

It was reported that biosynthesis of 99 starts with orsellinaldehyde from PKS-PkfA, which undergoes hydroxylation, one phenolic OH methylation, and prenylation to produce 197. Subsequently, hydroxylation of 197 yields 198 [49]. It was hypothesized that 198 is oxidized to produce asperugin, and then it is transformed into aspernidine A (99) through a series of steps [49] (Scheme 4).

From the red alga Polysiphonia scopulorum var. villum-associated A. nidulans EN-330, two new indole diterpenes are produced: 19-hydroxypenitrem A (93) and 19-hydroxypenitrem E (94), which are chlorinated and dechlorinated indole diterpenoids, respectively, along with known congeners 95 and 96, which were purified from the EtOAc cultures and acetone extracts by SiO₂/Sephadex LH-20/HPLC and characterized by NMR and CD analyses. These metabolites feature an indole skeleton produced from a tryptophan precursor (indole-3-glycerol-phosphate) and geranyl-geranyl diphosphate-derived cyclic diterpenoid framework. Penitrem A (95) belongs to a rare tremorgenic mycotoxins group that has a C-19 skeleton fused to C-2 and C-3 of the indole moiety. Compound 93 is like 95, but it has C19-oxygenated quaternary carbon instead of the methine in 95. Both 93 and 94 are 19S/22S/31R/32S configured. In the brine shrimp assay, 93–96 possessed potent cytotoxic effectiveness (LD₅₀s 3.2, 4.6, 1.7, and 8.7 μM, respectively), in comparison to colchicine (LD₅₀ 10.7 μM), where 93 and 95 were more powerful than 94, indicating that the C-6 Cl-substitution boosted the activity, while the 19-OH group suppressed it (93 vs. 95) [38]. In the assay for antibacterial activity against aquatic- (E. tarda and V. anguillarum) and human-pathogens (E. coli and S. aureus), 93–95 demonstrated moderate antimicrobial potential vs. E. tarda, V. anguillarum, E. coli, and S. aureus (MICs ranged from 16 to 64 μg/mL) [38].

From Annelida Whitmania pigra-associated A. nidulansi, aspernidines F–H (102–104), new prenylated isoindolinone alkaloids were purified and characterized utilizing SiO₂/Sephadex LH-20/HPLC and spectral/ECD analyses, respectively. They possess a C5-linked C15 side chain. Compounds 103 and 104 exhibited moderate cytotoxic capacity on A-549, HL-60, SMMC-7721, SW-480, and MCF-7 (IC₅₀s ranged from 4.77 to 33.03 μM) compared to cis-platin (IC₅₀ 3.22–22.96 μM). It was observed that 104 exhibited powerful inhibitory capacity vs. SW-480 cells (IC₅₀s 4.77 μM) compared to cis-platin (IC₅₀s 18.01 μM) [33].

In 2016, novel meroterpenoids, emericellolides A–C (105–107) and emeriphenolicins E–G (108–110), with an isoindolone nucleus were separated from an A. nidulans HDN12.249 EtOAc broth extract isolated from Tamarix chinensis leaves that were obtained from Laizhou Bay using SiO₂/RP-18/Sephadex LH-20/HPLC. Compounds 105–107 are characterized by an unparalleled macrolide skeleton consisting of an isoindolone moiety, an uncommon L-glutamate unit, and a sesquiterpene unit, while emeriphenolicins E–G (108–110) are rare isoindolone-based meroterpenoids with two farnesyl units linked to the isoindolone unit. These metabolites were structurally elucidated using NMR, MS, Mo₂(AcO)₄-induced ECD, chemical conversion, and Marfey’s method. In the SRB assay, only 108 exhibited selective potential vs. A549, HeLa, and HCT-116 (IC₅₀s 12.04, 4.77, and 33.05 μM, respectively); however, the others were ineffective (IC₅₀ > 50 μM) [39]. It was proposed that these metabolites were produced from asperugin A or B as an intermediate (Scheme 5). Further, farnesyl and L-glutamate units are formed through additional post-modifications, such as oxidation, methylation, and intra-molecular esterification [39].

3.4.5. Other Nitrogenous Compounds

Compound 111 was purified from cultured A. nidulans MeOH extract using alumina CC and crystallization from water. This compound had cytotoxic capacity vs. KB cells (endpoint value of 10–25 μ/mL and lethal endpoint of 50–100 μ/mL) [67], as well as inhibition of HCV NS3/4A protease (IC₅₀ 24.5 μg/mL), compared with HCV-12 (IC₅₀ 1.5 μg/mL), in addition to its potent cytotoxicity with inhibition zone difference of 100–200 mm vs. L1210, CCRF-CEM, colon 38, H-125, and HEP-G2 in the disc diffusion assay [47] (Figure 10).

The cerebroside, flavuside B (113), reported from orange peel-associated E. nidulans, had no antimalarial, antimicrobial, or antileishmanial capacities [68] (Table 8).

3.5. Peptides

Diverse strategies have evolved to take advantage of the biosynthetic stockpile of fungi. Various strategies are reported to better utilize the BGC (biosynthetic genes cluster) of this fungus.

The identification of aspercryptins (116–133), a new family of lipopeptides via prohibition of histone deacetylase (HDACi) in A. nidulans, was reported. They were discovered by NMR and MS/MS metabolite screening (Figure 11, Figure 12, Figure 13 and Figure 14). These metabolites are six-amino-acid peptides, having two non-canonical α-amino acids derived from saturated C12 and C8 fatty acids and a C-terminal alcohol [69] (Table 9). Hence, HDACi could be utilized for finding out new metabolites, even from fungal species that were intensively investigated.

3.6. Terpenoids and Sterols

Terpenoids and sterols are among the metabolites reported from E. nidulans that are derived from mevalonate via a key step of cyclization and elimination reaction, respectively.

The engineered A. nidulans biosynthesized 134, which was extracted using ASE (accelerated solvent extraction) and purified by HPLC (Table 10). In the DPPH assays, it had more powerful antioxidant potential than beta-carotene; however, it had no antimicrobial or anti-Leishmanial (50 µM) potential [71].

In 1983, β-amyrin was the first triterpenoid separated from A. nidulans [73]. From Whitmania pigra (Annelida, segmented worm)-associated A. nidulans, new sesterterpenoids, niduterpenoids A (136) and B (137), were reported that were purified from the EtOH culture extract by SiO₂/Sephadex LH-20/HPLC (Figure 15). These metabolites were distinguished by a highly congested 5/5/5/5/3/5 hexacyclic skeleton without unsaturated functional groups, based on spectral and X-ray analyses [40]. They were assessed for their ERα (estrogen receptor α) inhibitory and cytotoxic potential vs. MCF-7 in the MTT assay. Compound 136 had no obvious cytotoxic potential, even at 80 μM, while it abolished the 17-estradiol-induced cell proliferation (IC₅₀ 11.42 μM) in a dose-based way. Molecular docking revealed that 136 and 137 fitted well with the ERα ligand-binding site and partially occupied the lasofoxifene (potent Er modulator) whole pocket. They formed key H-bonds with Arg346/Glu353/Met295 and a highly hydrophobic envelope with Leu298/Phe356/Phe377/Met294/Leu354. These findings indicated 136 was a potential ERα antagonist that required further studies [40].

These metabolites are the first reported sesterterpenes with a hexacyclic ring system having an uncommon cyclopropane moiety (Scheme 6). It was proposed that they were biosynthesized from GFPP through various cyclization and Wagner–Meerwein alkyl shift and hydride reactions, producing the X (key intermediate) with a hexacyclic 5/5/5/5/3/5 framework. Additional oxidation reactions result in 136 and 137 [40].

Compounds 138, 139, and 142 are meroterpenoids separated from a cold spring, deep-sea-sediment-associated strain that had no antimicrobial capacity vs. aquatic/human bacteria and pathogenic plant fungi [31].

The separation of new metabolites 145 and 148–150 was reported, in addition to 146, 151–154, and 156 from the EtOAc extract of the fungus A. nidulans, utilizing SiO₂/Sephadex LH-20/HPLC and elucidated by spectral, ECD, and X-ray analyses (Figure 16).

These metabolites were assessed for cytotoxic potential in vitro vs. the PC12 cell line in the MTT assay. Only 145 possessed moderate potential (IC₅₀ 7.34 µM) compared to doxorubicin (IC₅₀ 5.71 µM) [41]. Compound 167, reported from the EtOAc broth extract of Emericella nidulans, was mildly active as an HCV inhibitor (IC₅₀ 47.0 μg/mL) relative to HCV-12 (IC₅₀ 1.5 μg/mL) [47] (Figure 17, Table 11).

3.7. Lactones and Furanones

A new metabolite, 172, was separated from the acetone culture extract of A. nidulans IFO6398 by SiO₂ CC using benzene as eluent. It featured two mono-substituted phenyl and maleic anhydride moieties; this compound was assigned by spectral analyses. In the radish seedlings bioassay, 172 accelerated root elongation (Conc. 30 and 100 g/L, respectively), while it had no notable influence on the hypocotyl elongation at the same concentrations. Moreover, 172 boosted root elongation and prohibited hypocotyl growth (Conc. 100 mg/L) in the lettuce seedling bioassay [75]. Compound 179, separated from the A. nidulans IFO6398 acetone extract, boosted root elongation (Conc. 30 g/L) and showed no notable effect on lettuce seedling growth (Conc. 3, 10, 30, and 100 mg/L) in the radish and lettuce seedling bioassays, respectively [75] (Table 12).

Microperfuranone (173), purified and characterized from E. nidulans var. acristata, had no antimicrobial, cytotoxic, and immune-stimulating activity [43], while 173 and 174 had antimicrobial potential against aquatic, human, and plant pathogens (MICs ranged from 4 to 64 μg/mL), whereas 173 presented notable effectiveness vs. E. ictarda (MIC 4 μg/mL) compared to chloramphenicol (MIC 2 μg/mL) [31] (Figure 18).

3.8. Polyketides and Glycerides

A new polyketide, koninginin H (187), together with 184–186 and 193–196, was reported from E. nidulans isolated from an orange peel (Figure 19, Table 13). Compound 187 belongs to the koninginin class of metabolites that was encountered in the Trichoderma genus [68]. An antimicrobial assessment of these metabolites vs. a panel of micro-organisms revealed that only 184 had good antifungal potential vs. C. neoformans (IC₅₀ 4.9 µg/mL) [68].

New metabolites, emeriones A-C (190–192), were purified from an EtOH extract of the culture broth of endophytic E. nidulans, obtained from Whitmania pigra by SiO₂/Sephadex LH-20/HPLC. These metabolites are high-methylated polyketides with 3,6-dioxabicyclo[3.1.0]hexane and bicyclo[4.2.0]octene functionalities and were characterized using spectroscopic, X-ray, and CD analyses as well as ECD calculations. Compounds 190 and 191 are similar but differ in their configuration at the C9, C12, and C13 epoxy rings, possessing 2R/3R/4S/5S/8R/9S/12R/13S/14S/15S/16S/17R and 2R/3R/4S/5S/8S/9R/12S/13R/14R/15R/16S/17R configurations, respectively. Moreover, 192 has an extra peroxide bridge that results in an unusual 7,8-dioxatricyclo[4.2.2.02,5]decene scaffold construction. The NO production inhibitory efficacy of 190 and 191 was tested on LPS-mediated NO production in RAW264.7 using a CCK-8 assay. Interestingly, 190 demonstrated inhibition potential vs. NO production with a percent inhibition of NO production of 68.3% at a concentration of 10.0 μM, compared to indomethacin (with a percent inhibition of NO production of 84.2%, Conc. 40 μM); however, 191 had no effectiveness, although it possesses the same structure as 190 and differs only in the bicyclo[4.2.0]octane core absolute configuration [80]. They were assumed to be synthesized from methylmalonyl CoA (9 molecules) and acetyl-CoA (one molecule) by polyketide synthase to produce I (Scheme 7), which generates II via a Payne rearrangement that features a 3,6-dioxabicyclo[3.1.0]hexane moiety (Scheme 7).

An octatomic ring is then formed through 8π electrocyclization and double bond isomerization to produce IV and V, which undergo 6π electrocyclizations to yield VI and VII, with a pair of mirror-image bicyclo[4.2.0]-octene frameworks. Further, 190 and 191 are created through an additional C-12 double bond epoxidation, while 192 is formed through a Diels–Alder reaction between an O₂ molecule and a bicyclo[4.2.0]octene core (Scheme 7) [80].

3.9. Other Metabolites

Asperbenzaldehyde (199) with an aromatic ring represents a new class of metabolites with tau aggregation inhibition potential. Moreover, its modified derivatives displayed noticeable lipoxygenase inhibition, suggesting its derived metabolites could exhibit dual activity [54].

The mycelia acetone extract of mutant A. nidulans LO2955 cultured on liquid lactose produced 202 (amount ≈200 mg/L), which was not found in such amounts in the wild strain culture. This compound had lipoxygenase-1 inhibition (IC₅₀ 97.2 μM) [42].

Asperoxide A (206), a new acyclic peroxide analog, and 203 were biosynthesized by A. nidulans SD531 obtained from cold spring, deep-sea sediment in the South China Sea by SiO₂/RP-18 CC and characterized by NMR and MS analyses [31] (Figure 20, Table 14). Their antimicrobial potential was examined vs. various aquatic/human bacteria and pathogenic plant fungi using a serial dilution technique. Compound 206 demonstrated antimicrobial effectiveness vs. V. harveyi, A. hydrophilia, V. parahaemolyticus, and E. tarda (MICs ranged from 16 to 64 μg/mL) [31].

4. Bioactivities of A. nidulans Extracts

The extract of E. nidulans var. acristata displayed cytotoxic potential vs. different cell lines (mean IC₇₀ of 8.30 µg/mL) [43]. A. nidulans EtOAc extract culture broth had only moderate antibacterial effectiveness vs. B. megaterium [47]. It also (Conc. 30 μg/disc) exhibited selectivity vs. HEP-G2, compared with CCRF-CEM and CFU-GM, and potent inhibitory activity vs. HCV NS3/4A protease (IC₅₀ 30.0 μg/mL) [47]. Rhizophora stylosa-associated A. nidulans MA-143 exhibited antibacterial and brine shrimp lethality potential [34]. E. nidulans MFW39 mycelium extract (IC₅₀ 21.9 μg/mL) was found to have a more potent cytotoxic effect vs. the T47D cell line than broth extract (IC₅₀ 169.3 μg/mL) [36]. Nyctanthes arbor-tristis-associated A. nidulans extracts and fractions had moderate to potent growth inhibitory potential against NCI-H460, MCF-7, and HeLa cell lines in the SRB, where broth extract (LC₅₀ 95.0 and IC₅₀ 10.0 μg/mL) was most potent vs. HeLa, whereas mycelium petroleum ether insoluble fraction was most powerful vs. MCF-7 and NCI-H460 (IC₅₀ 18.0 and 10.0 μg/mL, respectively) [53].

5. Importance of A. nidulans and Its Enzymes

Enzymes have attracted growing interest because of their prevalent industrial applications in various fields, including pharmaceuticals, food, chemicals, and energy [81]. They can provide a cost-efficient and more efficacious process for industrial manufacturing, in comparison to chemical catalysts, since they are quite specific, eco-friendly, and function under mild conditions [82]. Therefore, there is a marked research direction towards producing enzymes with high yields to fulfill the increased industrial demand, as well as reducing the costs of enzyme production medium, isolation, and purification. In this regard, interest has been directed towards fungi as a prolific pool of enzymes.

In 2020, a review by Kumar summarized the published studies on the potential of A. nidulans as a producer of varied enzymes that have applications in diverse industrial processes [28]. Thus, in this work, the recent reports on A. nidulans’s enzymes are highlighted.

Two genes encoding β-isopropyl-malate dehydrogenase and six genes encoding BCAA (branched-chain amino acids; isoleucine, leucine, and valine) aminotransferase, which catalyze the leucine penultimate step and the BCAA final step biosynthesis, respectively, were identified utilizing A. nidulans genome sequence searches [83]. Fungal biosynthesis of BCAA is substantial enough for these fungi to cause disease in plants and human hosts. It is worth mentioning that humans lack the enzymes accountable for BCAA production; therefore, these enzymes could be a potential target of antifungal agents.

5.1. Aryl Alcohol Oxidase

AAO (Aryl alcohol oxidase) is an H₂O₂-providing extracellular enzyme that belongs to the glucose–ethanol–choline oxidoreductase. It converts aromatic alcohols to aldehydes and provides H₂O₂ for peroxidases to degrade lignin [84]; hence, it has a considerable function in lignin depolymerization, particularly in lignin polymer oxidation for the generation of fuels and chemicals [85].

A cost-effective medium for AAO high-yield production by recombinant A. nidulans was developed in a submerged culture that consisted of CSL (corn steep liquor), which is an inexpensive and rich source of nitrogen, vitamins, and minerals, in addition to NaNO₃ (13.8 g/L), CSL (26.4 g/L), and maltose (61.0 g/L). It was observed that the highest achieved AAO capacity was 1021 U/L, with a 0.75 g/L protein concentration [86].

5.2. Laccases

Laccases, belonging to the multi-copper oxidase family, accelerate the O₂ four-electron reduction to water with diverse non-phenolic and phenolic compound oxidation [16,87,88,89]. These features give them varied industrial applicability, including wine stabilization, denim-bleaching, detoxification and decolorization of dye-containing textiles and lignin-linked compound effluents, and pulp bio-bleaching for the paper industry [16,87,88,89].

From A. nidulans TTF-6, purified and crude laccases were employed to decolorize different dyes (e.g., methyl orange, Congo red, Victoria blue, methyl red, methyl violet, bromophenol blue, and Coomassie blue). At 40 °C, it was found that the crude enzyme needed a longer time treatment time (7 days) in comparison to the purified one (up to 48 h). Among the tested dyes, methyl red (azo dye) was taken away slowly relative to Victoria and Coomassie blue (blue-triphenylamines). A high decolorizing rate was noted at 40 °C compared to 20 °C [90].

5.3. Pectate Lyases and Nitroreductases

Pectin, a primary component of fibers, vegetables, cereals, and fruits, has a high molecular weight and is a complicated, acidic- and heterogeneous-structured polysaccharide that is hydrolyzed by pectinolytic enzymes. These enzymes have assorted industrial applicability in wine and fruit juice liquefaction, extraction, and clarification; in the fabric industry for separating plant fibers such as jute, flax, and hemp; in cotton fabric bio-preparation; in paper manufacture, treating paper and pulp mill effluents; and in amending black tea’s quality [91]. These enzymes represent 25% of the global sales of food enzymes [92]. Among them, pectate lyases act on the pectate core internal α-1,4-linkage, having a crucial function in pectin breaking down.

In 2022, AnPL9 pectate lyase, a member of PL9 (polysaccharide-lyase family-9), was characterized and purified from A. nidulans that was expressed in Pichia pastoris [93]. It is the first stated fungi derived from the PL9 pectate lyase family. AnPL9 revealed high potential on GH (homogalacturonan), the pectin from apple and citrus peel. It converted tetra-galacturonic acid to digalact-uronic acid and 4,5-unsaturated digalacturonic acid. Additionally, AnPL9 possessed marked stability at 6–11 pH with a more than 4 polymerization degree of HG oligo-saccharides, indicating AnPL9 is beneficial for bio-technological usage in paper, food, and textile manufacturing [93].

Nitroreductases are implicated in nitro-heterocyclic and -aromatic compounds and quinone reduction. They have received marked attention for their usage in environmental pollutant biodegradation [94]. It was reported that A. nidulans produced nitroreductase boosted by menadione [95].

5.4. Xylanases

Xylanases are accountable for hydrolyzing xylan by cleaving the β-1,4 link, which is a main constituent of hemicellulose. They have remarkable applicability in various fields, such as food, paper and pulp, and bio-fuel industries, as well as in effluent and agro-waste treatment.

A study reported that optimized xylanase (1250 U/mL) production, with a productivity of 313 U/mL/day by recombinant A. nidulans in a 3 L stirred tank reactor, was a 400 rpm agitation rate and 2 vvm aeration rate utilizing batch fermentation. Further, the enzyme production elevated to 327 U/mL/day and 373 U/mL/day and maximum capacity increased to 1410 and 1572 U/mL, respectively, with repeated-batch and fed-batch fermentation, respectively [96].

5.5. Meta-Cresol Production

meta-Cresol is an industrially beneficial compound that is mainly generated by chemical means from fossil sources. It has been widely employed for farm chemicals, spices, dyes, and medicine production [97]. It is also a synthetic precursor for thymol, alpha-tocopherol, menthol, fenthion, sumithion, permethrin, diphenylamine, pressure-sensitive fuel, resin plasticizer, eikonogen, etc. Its mainstream production strategies involve extraction from coal tar and chemical means as cumene acidolysis and toluene-chlorination hydrolysis [98]. However, these strategies have apparent disadvantages: tiresome but unavoidable steps of m-cresol separation from the p-, m-, and o-cresol mixtures, environmental pollution, high costs, and less purity and titer [99].

The m-cresol overproduction utilizing modified A. nidulans FGSC no. A1145∆ST∆EM was reported, which gave a gram-level titer utilizing starch (carbon source) [97]. Various strategies were carried out to increase m-cresol production, such as gene multiplication and promotor engineering, resulting in an increase to m-cresol production titers of 1.29 g/L and 2.03 g/L in shaking flasks and fed-batch culture, respectively. A. nidulans A1145∆ST∆EM possessed better resistance to m-cresol than yeast, as it grew in the liquid medium, producing up to 2.5 g/L m-cresol. Thus, A. nidulans could be further engineered for m-cresol bio-production for industrial purposes [97].

5.6. Nanoparticles Synthesis

Metallic oxide NPs (nanoparticles) have extreme usage in supercapacitors, devices, batteries, and biosensors. Vijayanandan and Balakrishnan reported that A. nidulans is an efficient fungus for the synthesis of Co₃O₄ (cobalt oxide) NPs [100].

Additionally, the Co₃O₄ nanofluid synthesized employing Nothapodytes foetida-associated A. nidulans possessed good SAR (specific absorption rate), photothermal conversion efficiency, and a greater temperature gradient than water. The good solar energy absorption ability of this nanofluid indicates its convenience for direct-absorption solar thermal energy systems [101].

6. Conclusions

In the present work, 206 metabolites of varied classes, including different types of alkaloids, xanthines, quinones, depsidones, lactones, benzophenones, furanones, terpenoids, sterols, cerebrosides, fatty acids, polyketides, and others were characterized from A. nidulans and its teleomorph from 1953 to November 2022. The fungus has been collected from various sources, such as sea sediments, sponges, ascidians, algae, endophytes, soil, worms, and cultures.

Notably, a great number of metabolites were described in 2019 (39 compounds), 2013 (34 compounds), and 2016 (30 compounds).

Alkaloids of diverse types are the main metabolites reported from this fungus. They have been investigated for different biocapacities, such as antimicrobial, cytotoxic, anti-inflammation, antioxidant, antiviral, and Erα activities. Although there is a large number of reported metabolites, a limited number of them have been evaluated for their bioactivities.

Compounds 136 and 137 provide promising target molecules for further research as ERα (estrogen receptor α) inhibitors. Interestingly, 25 and 30 demonstrated marked tau aggregation inhibitory potential; therefore, they could be lead compounds for developing tau aggregation inhibitors in Alzheimer’s disease and neurodegenerative tauopathies. Additionally, 36, 56, and 92 had potent antimicrobial potential as lead metabolites for antimicrobial agents. Moreover, 83, 84, 93, 95, and 104 revealed marked cytotoxic efficacies vs. different cell lines. Further in vivo and mechanistic investigations to elucidate and validate possible mechanisms for the active metabolites are needed, exploring the possible bioactivities of unevaluated metabolites using molecular dynamic and docking investigation.

It was found that metabolic-biosynthesis pathway engineering revealed the usefulness of creating profuse numbers of fascinating metabolites. Additionally, modifying the culture parameters and conditions affected metabolite production, such as ethanol stress. Several studies reported the usage of silent gene activation strategies, such as optimizing culture conditions (O₂ concentration, pH, and temperature), adding chemical elicitors (e.g., HDACi), and co-culturing with other microbes. These strategies could open a new direction for regulating the production of metabolites and play a pronounced role in elucidating cryptic natural metabolites that will assist in the future discovery of new metabolites. Further investigation of biosynthetic pathways of these metabolites is a prerequisite for allowing the reasonable engineering or refactoring of these pathways for industrial purposes. In addition, identifying genes accountable for these metabolites’ formation could provide a chance for exploring the genetic potential of this fungus to discover novel metabolites. Therefore, using combined techniques such as genome mining, bio-informatics, fusion PCR, CRISPR (Clustered-Regularly-Interspaced Short-Palindromic Repeats), expression profiling, and culture manipulation has become progressively efficient in discovering and activating silent clusters in A. nidulans [102].

Author Contributions

Conceptualization, S.R.M.I. and G.A.M.; methodology, S.R.M.I., G.A.M. and S.G.A.M.; software, S.A.F. and K.F.G.; writing—original draft preparation, S.R.M.I., S.G.A.M. and G.A.M.; writing—review and editing, S.R.M.I., G.A.M., S.A.F. and K.F.G. resources, S.A.F. and K.F.G. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

BEL-7402	Human hepatocellular carcinoma cell line
C28	Human colon Cell Line
CCRF-CEM	Human leukemia cell line
CCK-8	Cell counting kit-8
CD	Circular dichroism
ECD	Electronic circular dichroism
EtOH	Ethanol
EtOAc	Ethyl acetate
H-125	Human lung cancer cell line
HCT-116	Human colon cancer cell line
HepG2	Human hepatocellular liver carcinoma cell line
HeLa	Human cervical epitheloid carcinoma cell line
HL-60	Human promyelocytic leukemia cell line
HPLC	High-performance liquid chromatography
IC₅₀	Half-maximal inhibitory concentration
K562	Human myelocytic leukemia cell line
KB	Human oral epidermoid carcinoma cell line
L1210	Mouse lymphocytic leukemia cell line
LD₅₀	Half maximal lethal concentration
LPS	Lipopolysaccharide
MCF-7	Human breast adenocarcinoma cell line
MDA-MB-231	Human breast cancer cell line
MIC	Minimum inhibitory concentrations
MS	Mass spectrometry
MTT	3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
NCI-H460	Human lung cancer cell line
NMR	Nuclear magnetic resonance
NO	Nitric oxide
PC12	Rat brain cancer cell line
RP-18	Reversed phase-18
SRB	Sulforhodamine B
SiO₂ CC	Silica gel column chromatography
T47D	Human breast cancer cell line
TLC	Thin layer chromatography
WiDr	Human colon adenocarcinoma cell line

Footnotes

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Figures, Schemes and Tables

Figure 1. Structures of benzophenones (1–10) reported from Aspergillus nidulans.

Scheme 1. Biosynthetic pathways of compounds 3, 7, 8, and 10 from chrysophanol (29) [43].

Figure 2. Structures of xanthones (11–21) reported from Aspergillus nidulans.

Scheme 2. Biosynthetic pathways of 12, 14, 16, and 17 [45].

Figure 3. Structures of quinones (22–34).

Figure 4. Structures of quinones (35–47).

Figure 5. Structures of depsidones (48–51) and biphenyl ethers (52–60).

Figure 6. Structures of quinoline alkaloids (61–73).

Scheme 3. Biosynthetic pathways of aspoquinolones A–D (61–64) [62].

Figure 7. Structures of quinazolinone (74–77), pyrazine (78–81), dioxopiperazine (82 and 83), and phenazine (84) alkaloids.

Figure 8. Structures of indole (85–97) alkaloids.

Figure 9. Structures of isoindole (98–110) alkaloids.

Scheme 4. Biosynthetic pathways of aspernidine A (99) [49].

Scheme 5. Biosynthesis pathways of 105–110 from asperugin A or B [39].

Figure 10. Structures of other nitrogenous compound (111–113) alkaloids.

Figure 11. Structures of peptides (114–119).

Figure 12. Structures of peptides (120–125).

Figure 13. Structures of peptides (126–129).

Figure 14. Structures of peptides (130–133).

Figure 15. Structures of terpenoids (135–144).

Scheme 6. Biosynthesis of niduterpenoids A (136) and B (137) from GFPP [40].

Figure 16. Structures of sterols (145–155).

Figure 17. Structures of sterols (156–167).

Figure 18. Structures of furan (168–178) and pyran (179–188) derivatives.

Figure 19. Structures of polyketides (189–193) and glycerides (194–196).

Scheme 7. Biosynthesis of emeriones A–C (190–192) [81].

Figure 20. Structures of other metabolites (197–206).

Table 1

Biological activity of reported metabolites from Aspergillus nidulans.

Compound Name	Biological Activity	Assay, Organism or Cell Line	Biological Results		Ref.
Compound Name	Biological Activity	Assay, Organism or Cell Line	Compound	Positive Control	Ref.
Isosecosterigmatocystin (15)	Antimicrobial	Microplate/Edwardsiella ictaluri	16.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[30]
		Serial dilution/Edwardsiella ictarda	16.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[31]
Sterigmatocystin (18)	Antimicrobial	Serial dilution/Vibrio parahaemolyticus	64.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
Versicolorin C (35)	Antimicrobial	Microplate/Escherichia coli	1.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[30]
		Microplate/Micrococcus luteus	32.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[30]
		Microplate/Vibrio anguillarum	4.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[30]
		Microplate/Vibrio alginolyticus	16.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[30]
		Microplate/Edwardsiella ictaluri	8.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[30]
		Microplate/Vibrio parahaemolyticus	1.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[30]
Isoversicolorin C (36)	Antimicrobial	Microplate/Escherichia coli	32.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[30]
		Microplate/Micrococcus luteus	16.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[30]
		Microplate/Vibrio vulnificus	64.0 µg/mL (MIC)	Chloramphenicol 8.0 µg/mL (MIC)	[30]
		Microplate/Vibrio alginolyticus	1.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[30]
		Microplate/Edwardsiella ictaluri	4.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[30]
		Microplate/Vibrio parahaemolyticus	32.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[30]
Violaceol I (52)	Antimicrobial	Microdilution/Bacillus subtilis	13.0 µg/mL (MIC)	Chloramphenicol 6.3 µg/mL (MIC)	[32]
Violaceol II (53)	Antimicrobial	Microdilution/Bacillus subtilis	50 µg/mL (MIC)	Chloramphenicol 6.3 µg/mL (MIC)	[32]
Diorcinol (54)	Antimicrobial	Microdilution/Bacillus subtilis	100.0 µg/mL (MIC)	Chloramphenicol 6.3 µg/mL (MIC)	[32]
Cordyol C (55)	Antimicrobial	Microdilution/Bacillus subtilis	100.0 µg/mL (MIC)	Chloramphenicol 6.3 µg/mL (MIC)	[32]
Gibellulin A (56)	Antimicrobial	Serial dilution/Aeromonas hydrophilia	4.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Colletotrichum gloeosporioides	4.0 µg/mL (MIC)	Amphotericin B 0.5 µg/mL (MIC)	[31]
		Serial dilution/Edwardsiella ictarda	2.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[31]
		Serial dilution/Edwardsiella tarda	4.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Escherichia coli	8.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[31]
		Serial dilution/Vibrio alginolyticus	8.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Vibrio harvey	4.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[31]
		Serial dilution/Vibrio parahaemolyticus	16.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
Aspoquinolone E (65)	Cytotoxicity	MTT/HL-60	29.15 µM (IC₅₀)	cis-platin 3.22 µM (IC₅₀)	[33]
		MTT/A-549	3.50 µM (IC₅₀)	cis-platin 13.17 µM (IC₅₀)	[33]
		MTT/MCF-7	24.50 µM (IC₅₀)	cis-platin 22.96 µM (IC₅₀)	[33]
Aniduquinolone B (68)	Cytotoxicity	Brine shrimp lethality/Artemia salina	7.1 μM (LD₅₀)	Colchicine 88.4 μΜ (LD₅₀)	[34]
6-Deoxyaflaquinolone E (70)	Cytotoxicity	Brine shrimp lethality/Artemia salina	4.5 μM (LD₅₀)	Colchicine 88.4 μΜ (LD₅₀)	[34]
Aflaquinolone A (73)	Cytotoxicity	Brine shrimp lethality/Artemia salina	5.5 μM (LD₅₀)	Colchicine 88.4 μΜ (LD₅₀)	[34]
Aniquinazoline A (74)	Cytotoxicity	Brine shrimp lethality/Artemia salina	1.27 μM (LD₅₀)	Colchicine 88.4 μΜ (LD₅₀)	[35]
Aniquinazoline B (75)	Cytotoxicity	Brine shrimp lethality/Artemia salina	2.11 μM (LD₅₀)	Colchicine 88.4 μΜ (LD₅₀)	[35]
Aniquinazoline C (76)	Cytotoxicity	Brine shrimp lethality/Artemia salina	4.95 μM (LD₅₀)	Colchicine 88.4 μΜ (LD₅₀)	[35]
Aniquinazoline D (77)	Cytotoxicity	Brine shrimp lethality/Artemia salina	3.42 μM (LD₅₀)	Colchicine 88.4 μΜ (LD₅₀)	[35]
Glulisine A (81)	Antimicrobial	Microplate/Edwardsiella ictaluri	64.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[30]
Emestrin (82)		MTT/T47D	1.8 μg/mL (IC₅₀)	-	[36]
		MTT/HepG2	4.2 μg/mL (IC₅₀)	-
		MTT/C28	2.6 μg/mL (IC₅₀)	-
		MTT/HeLa	13.8 μg/mL (IC₅₀)	-
Emestrin B (83)		MTT/T47D	0.16 μg/mL (IC₅₀)	-	[37]
		MTT/HeLa	1.56 μg/mL (IC₅₀)	-
		MTT/WiDr	and 1.02 μg/mL (IC₅₀)	-
3,3′-Diindolylmethane (91)	Antimicrobial	Serial dilution/Aeromonas hydrophilia	64.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Colletotrichum gloeosporioides	64.0 µg/mL (MIC)	Amphotericin B 0.5 µg/mL (MIC)	[31]
		Serial dilution/Edwardsiella tarda	64.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
Terrequinone A (92)	Antimicrobial	Serial dilution/Aeromonas hydrophilia	64.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Colletotrichum gloeosporioides	2.0 µg/mL (MIC)	Amphotericin B 0.5 µg/mL (MIC)	[31]
		Serial dilution/Edwardsiella tarda	16.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Escherichia coli	2.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[31]
		Serial dilution/Vibrio alginolyticus	2.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Vibrio harvey	64.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[31]
		Serial dilution/Vibrio parahaemolyticus	32.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
19-Hydroxypenitrem A (93)	Cytotoxicity	Brine shrimp lethality/Artemia salina	3.2 μM (LD₅₀)	Colchicine 10.7 μΜ (LD₅₀)	[38]
	Antibacterial	Well diffusion/Escherichia coli	16.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[38]
		Well diffusion/Edwardsiella tarda	16.0 µg/mL (MIC)	Chloramphenicol 16.0 µg/mL (MIC)	[38]
		Well diffusion/S. aureus	16.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[38]
		Well diffusion/Vibrio anguillarum	32.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[38]
19-Hydroxypenitrem E (94)	Cytotoxicity	Brine shrimp lethality/Artemia salina	4.6 μM (LD₅₀)	Colchicine 10.7 μΜ (LD₅₀)	[38]
	Antibacterial	Well diffusion/Escherichia coli	64.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[38]
		Well diffusion/Edwardsiella tarda	64.0 µg/mL (MIC)	Chloramphenicol 16.0 µg/mL (MIC)	[38]
Penitrem A (95)	Cytotoxicity	Brine shrimp lethality/ ArtemiArtemia salina	1.7 μM (LD₅₀)	Colchicine 10.7 μΜ (LD₅₀)	[38]
	Antibacterial	Well diffusion/Escherichia coli	16.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[38]
		Well diffusion/Edwardsiella tarda	16.0 µg/mL (MIC)	Chloramphenicol 16.0 µg/mL (MIC)	[38]
		Well diffusion/S. aureus	16.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[38]
		Well diffusion/Vibrio anguillarum	16.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[38]
Penijanthine A (96)	Cytotoxicity	Brine shrimp lethality/Artemia salina	8.7 μM (LD₅₀)	Colchicine 10.7 μΜ (LD₅₀)	[38]
Aspernidine G (103)	Cytotoxicity	MTT/HL-60	28.75 µM (IC₅₀)	cis-platin 3.22 µM (IC₅₀)	[33]
		MTT/MCF-7	28.31 µM (IC₅₀)	cis-platin 22.96 µM (IC₅₀)	[33]
		MTT/SW-480	21.67 µM (IC₅₀)	cis platin 18.01 µM (IC₅₀)	[33]
Aspernidine H (104)	Cytotoxicity	MTT/HL-60	15.81 µM (IC₅₀)	cis-platin 3.22 µM (IC₅₀)	[33]
		MTT/A-549	33.03 µM (IC₅₀)	cis-platin 13.17 µM (IC₅₀)	[33]
		MTT/SMMC-7721	17.17 µM (IC₅₀)	cis-platin 12.65 µM (IC₅₀)	[33]
		MTT/MCF-7	17.80 µM (IC₅₀)	cis-platin 22.96 µM (IC₅₀)	[33]
		MTT/SW-480	4.77 µM (IC₅₀)	cis-platin 18.01 µM (IC₅₀)	[33]
Emeriphenolicin E (108)	Cytotoxicity	SRB/HeLa	4.77 µM (IC₅₀)	Adriamycin	[39]
		SRB/A549	12.04 µM (IC₅₀)	Adriamycin	[39]
		SRB/HCT-116	33.05 µM (IC₅₀)	Adriamycin	[39]
Niduterpenoid A (136)	ERα inhibitors	MCF-7/MTT	11.42 µM (IC₅₀)	-	[40]
(7Z,9Z,17Z)-,2α,3β-dihydroxypregna-7,9,17 (20)-trien-18-al (145)	Cytotoxicity	MTT/PC12	7.34 µM (IC₅₀)	Doxorubicin 5.71 µM (IC₅₀)	[41]
Microperfuranone (173)	Antimicrobial	Serial dilution/Colletotrichum gloeosporioides	32.0 µg/mL (MIC)	Amphotericin B 0.5 µg/mL (MIC)	[31]
		Serial dilution/Edwardsiella ictarda	4.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[31]
		Serial dilution/Edwardsiella tarda	32.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Escherichia coli	32.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[31]
		Serial dilution/Vibrio harvey	16.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[31]
		Serial dilution/Vibrio parahaemolyticus	32.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
9-Hydroxymicroperfuranone (174)	Antimicrobial	Serial dilution/Colletotrichum gloeosporioides	64.0 µg/mL (MIC)	Amphotericin B 0.5 µg/mL (MIC)	[31]
		Serial dilution/Edwardsiella tarda	32.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Escherichia coli	64.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[31]
		Serial dilution/Vibrio harvey	16.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[31]
Curvularin (189)	Antimicrobial	Serial dilution/Edwardsiella ictarda	32.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[31]
6-((S,3E,5E)-5,7-Dimethyl-2-oxonona-3,5-dien-1-yl)-2,4-dihydroxy-3-methylbenzaldehyde (202)	Lipoxygenase-1 inhibition	Spectrophotometric/Soybean lipoxygenase 1	97.2 µM (IC₅₀)	-	[42]
Lecanoric acid (203)	Antimicrobial	Serial dilution/Aeromonas hydrophilia	32.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Edwardsiella ictarda	32.0 µg/mL (MIC)	Chloramphenicol 2.0 µg/mL (MIC)	[31]
		Serial dilution/Escherichia coli	16.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[31]
		Serial dilution/Vibrio harvey	8.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[31]
		Serial dilution/Vibrio parahaemolyticus	4.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
Asperoxide A (206)	Antimicrobial	Serial dilution/Aeromonas hydrophilia	32.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Edwardsiella tarda	16.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]
		Serial dilution/Vibrio harveyi	32.0 µg/mL (MIC)	Chloramphenicol 1.0 µg/mL (MIC)	[31]
		Serial dilution/Vibrio parahaemolyticus	64.0 µg/mL (MIC)	Chloramphenicol 0.5 µg/mL (MIC)	[31]

Table 2

Benzophenones reported from Aspergillus nidulans.

Compound Name	Mol. Wt. *	Mol. Formula *	Host (Part, Family)/Location	Ref.
Monodictyphenone (1)	288	C₁₅H₁₂O₆	Cultured	[44]
Arugosin F (2)	272	C₁₅H₁₂O₅	Cultured	[45]
Arugosin H (3)	356	C₂₀H₂₀O₆	Cultured	[45]
	-	-	Green alga, Sardinia, Italy, Mediterranean Sea	[43]
Arugosin I (4)	340	C₂₀H₂₀O₅	Cultured	[45]
Nidulalin B (5)	302	C₁₆H₁₄O₆	Cultured	[46]
1(3H)-Isobenzofuranone, 3-(2,6-dihydroxyphenyl)-4-hydroxy-6-methyl (6)	272	C₁₅H₁₂O₅	Cultured	[44]
Arugosin A (7)	424	C₂₅H₂₈O₆	Cultured	[45]
	-	-	Green alga, Sardinia, Italy, Mediterranean Sea	[43]
Arugosin B (8)	424	C₂₅H₂₈O₆	Cultured	[45]
	-	-	Green alga, Sardinia, Italy, Mediterranean Sea	[43]
Arugosin C (9)	426	C₂₅H₃₀O₆	Deep-sea sediment, South China Sea	[31]
Arugosin G (10)	492	C₃₀H₃₆O₆	Green alga, Sardinia, Italy, Mediterranean Sea	[43]

* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.

Table 3

Xanthones and quinones reported from Aspergillus nidulans.

Compound Name/Chemical Class	Mol. Wt. *	Mol. Formula *	Host (Part, Family)/Location	Ref.
Xanthones
9H-Xanthen-9-one, 8-hydroxy-1-(hydroxymethyl)-3-methyl (11)	256	C₁₅H₁₂O₄	Cultured	[44]
Variecoxanthone A (12)	340	C₂₀H₂₀O₅	Cultured	[44,45]
Paeciloxanthone (13)	324	C₂₀H₂₀O₄	Cultured	[44]
Emericellin (14)	408	C₂₅H₂₈O₅	Cultured	[44,45,48,49]
	-	-	Green alga, Sardinia, Italy, Mediterranean Sea	[43]
	-	-	Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt	[47,50]
Isosecosterigmatocystin (15)	362	C₁₈H₁₈O₈	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[30]
	-	-	Deep-sea sediment, South China Sea	[31]
Shamixanthone (16)	406	C₂₅H₂₆O₅	Cultured	[44,45,48,49]
	-	-	Green alga, Sardinia, Italy, Mediterranean Sea	[43]
	-	-	Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt	[50]
Epishamixanthone (17)	406	C₂₅H₂₆O₅	Cultured	[44,45,49]
Sterigmatocystin (18)	324	C₁₈H₁₂O₆	Cultured	[48,49,51]
	-	-	Green alga, Sardinia, Italy, Mediterranean Sea	[43]
	-	-	Soil, Hell Valley, Noboribetsu, Hokkaido, Japan	[52]
	-	-	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[30]
	-	-	Deep-sea sediment, South China Sea	[31]
	-	-	Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt	[47]
	-	-	Nyctanthes arbor-tristis (Oleaceae), Sabira	[53]
Demethylsterigmatocystin (19)	310	C₁₇H₁₀O₆	Cultured	[54]
1-Hydroxy-3-methylxanthone (20)	226	C₁₄H₁₀O₃	Nyctanthes arbor-tristis (Oleaceae), Sabira	[53]
Nidulalin A (21)	302	C₁₆H₁₄O₆	Cultured	[46]
Quinones
1,6,8-Trihydroxyxanthone (22)	256	C₁₄H₈O₅	Cultured	[55]
Emodin (23)	270	C₁₅H₁₀O₅	Cultured	[44,55]
2-Hydroxyemodin (24)	286	C₁₅H₁₀O₆	Cultured	[56]
2,ω-Dihydroxyemodin (25)	302	C₁₅H₁₀O₇	Cultured	[44]
ω-Hydroxyemodin (26)	286	C₁₅H₁₀O₆	Cultured	[44]
Aloe-emodin (27)	270	C₁₅H₁₀O₅	Cultured	[44]
Endocrocin (28)	314	C₁₆H₁₀O₇	Cultured	[44]
Chrysophanol (29)	254	C₁₅H₁₀O₄	Cultured	[44,45]
Asperthecin (30)	318	C₁₅H₁₀O₈	Cultured	[49,57]
3′-Hydroxyversiconol (31)	376	C₁₈H₁₆O₉	Cultured	[54]
Versiconol (32)	360	C₁₈H₁₆O₈	Cultured	[56]
Averantin (33)	372	C₂₀H₂₀O₇	Cultured	[56]
Norsolorinic acid (34)	370	C₂₀H₁₈O₇	Cultured	[55]
	-	-	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[30]
Versicolorin C (35)	340	C₁₈H₁₂O₇	Cultured	[48,51]
	-	-	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[30]
Isoversicolorin C (36)	340	C₁₈H₁₂O₇	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[30]
8-O-Methylversicolorin A (37)	352	C₁₉H₁₂O₇	Deep-sea sediment, western Pacific Ocean, China	[58]
Aversin (38)	368	C₂₀H₁₆O₇	Deep-sea sediment, western Pacific Ocean, China	[58]
Averufin (39)	368	C₂₀H₁₆O₇	Cultured	[48,51]
	-	-	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[30]
6-O-Methylaverufin (40)	382	C₂₁H₁₈O₇	Deep-sea sediment, western Pacific Ocean, China	[58]
6,8-Di-O-Methylaverufin (41)	396	C₂₂H₂₀O₇	Deep-sea sediment, western Pacific Ocean, China	[58]
Nidurufin (42)	384	C₂₀H₁₆O₈	Cultured	[51]
Ascoquinone A (43)	618	C₃₀H₁₈O₁₅	Cultured	[55]
Averufanin (44)	370	C₂₀H₁₈O₇	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[30]
Paeciloquinone E (45)	368	C₂₀H₁₆O₇	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[30]
cis-Emodinphysicon-bianthrone (46)	524	C₃₁H₂₄O₈	Cultured	[56]
trans-Emodin-physicon bianthrone (47)	524	C₃₁H₂₄O₈	Cultured	[56]

* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.

Table 4

Depsidone and diphenyl ethers reported from Aspergillus nidulans.

Compound Name/Chemical Class	Mol. Wt. *	Mol. Formula *	Host (Part, Family)/Location	Ref.
Depsidone
Nidulin (48)	443	C₂₀H₁₇Cl₃O₅	Cultured	[60]
Nor-nidulin (Ustin) (49)	427	C₁₉H₁₅Cl₃O₅	Cultured	[60]
Dechloro-nornidulin (50)	394	C₁₉H₁₆Cl₂O₅	Cultured	[61]
Trisdechloro-nornidulin (51)	326	C₁₉H₁₈O₅	Cultured	[61]
Diphenyl ethers
Violaceol I (52)	262	C₁₄H₁₄O₅	Cultured	[32]
Violaceol II (53)	262	C₁₄H₁₄O₅	Cultured	[32]
Diorcinol (54)	230	C₁₄H₁₄O3	Cultured	[32]
	-	-	Soil, Hell Valley, Noboribetsu, Hokkaido, Japan	[52]
	-	-	Deep-sea sediment, western Pacific Ocean, China	[58]
Cordyol C (55)	246	C₁₄H₁₄O₄	Cultured	[32]
Gibellulin A (56)	360	C₁₄H₁₂O₅	Deep-sea sediment, South China Sea	[31]
Gibellulin C (57)	274	C₁₅H₁₄O₅	Cultured	[57]
Gibellulin D (58)	274	C₁₅H₁₄O₅	Cultured	[57]
F9775 A (59)	396	C₂₁H₁₆O₈	Cultured	[54]
F9775 B (60)	396	C₂₁H₁₆O₈	Cultured	[54]

* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.

Table 5

Quinoline alkaloids reported from Aspergillus nidulans.

Compound Name	Mol. Wt. *	Mol. Formula *	Host (Part, Family)/Location	Ref.
Aspoquinolone A (61)	465	C₂₇H₃₁NO₆	Cultured	[62]
Aspoquinolone B (62)	465	C₂₇H₃₁NO₆	Cultured	[62]
Aspoquinolone C (63)	483	C₂₇H₃₃NO₇	Cultured	[62]
Aspoquinolone D (64)	483	C₂₇H₃₃NO₇	Cultured	[62]
Aspoquinolone E (65)	435	C₂₆H₂₉NO₅	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China	[33]
Aspoquinolone F (66)	435	C₂₆H₂₉NO₅	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China	[33]
Aniduquinolone A (67)	435	C₂₆H₂₉NO₅	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[34]
Aniduquinolone B (68)	453	C₂₆H₃₁NO₆	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[34]
Aniduquinolone C (69)	353	C₂₁H₂₃NO₄	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[34]
6-Deoxyaflaquinolone E (70)	269	C₁₆H₁₅NO₃	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[34]
Isoaflaquinolone E (71)	285	C₁₆H₁₅NO₄	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[34]
14-Hydroxyaflaquinolone F (72)	271	C₁₅H₁₃NO₄	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[34]
Aflaquinolone A (73)	433	C₂₇H₃₁NO₄	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[34]

* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.

Table 6

Quinazolinone, pyrazine, dioxopiperazine, and phenazine alkaloids reported from A. nidulans.

Compound Name/Chemical Class	Mol. Wt. *	Mol. Formula *	Host (Part, Family)/Location	Ref.
Quinazolinone alkaloids
Aniquinazoline A (74)	471	C₂₆H₂₅N₅O₄	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[35]
Aniquinazoline B (75)	473	C₂₆H₂₇N₅O₄	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[35]
Aniquinazoline C (76)	489	C₂₆H₂₇N₅O₅	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[35]
Aniquinazoline D (77)	430	C₂₂H₂₄N₄O₄	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[35]
Pyrazine alkaloids
Hydroxyaspergillic acid (78)	240	C₁₂H₂₀N₂O₃	Cultured	[63]
Neohydroxyaspergillc acid (79)	240	C₁₂H₂₀N₂O₃	Cultured	[63]
1-Hydroxy-3-sec-butyl-6-(1-hydroxy-l-methyl-propyl)-pyrazin-2-one (80)	240	C₁₂H₂₀N₂O₃	Cultured	[63]
Glulisine A (81)	223	C₁₁H₁₇N₃O₂	Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)	[30]
Dioxopiperazine alkaloids
Emestrin (82)	598	C₂₇H₂₂N₂O₁₀S₂	Soil, Hell Valley, Noboribetsu, Hokkaido, Japan	[36,52]
			Aplidium longithorax (Ascidin, Polyclinidae), Wakatobi Marine National Park, Southeast Sulawesi, Indonesia	[36]
Emestrin B (83)	630	C₂₇H₂₂N₂O₁₀S₃	Aplidium longithorax (Marine Ascidin, Polyclinidae), Wakatobi Marine National Park, Southeast Sulawesi, Indonesia	[37]
Phenazine alkaloids
5,10-Dihydrophenazine-1-carboxylic acid (84)	226	C₁₃H₁₀N₂O₂	Nyctanthes arbor-tristis Linn (Oleaceae), Sabira	[53]

* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.

Table 7

Indole and isoindole alkaloids reported from A. nidulans.

Compound Name/Chemical Class	Mol. Wt. *	Mol. Formula *	Host (Part, Family)/Location	Ref.
Indole alkaloids
N-Acetyl-6-hydroxy-DL-tryptophan (85)	262	C₁₃H₁₄N₂O₄	Cultured	[66]
N-Acetyl-6-benzyloxy-DL-tryptophan (86)	352	C₂₀H₂₀N₂O₄	Cultured	[66]
Ergotryptamine (87)	258	C₁₆H₂₂N₂O	Mutant strain cultured	[64]
N-methyl-4-dimethylallyltryptophan (88)	286	C₁₇H₂₂N₂O₂	Mutant strain cultured	[64]
(Z)-N-Methyl-5-(2-methylpropylidene)-1,3,4,5-tetrahydrobenzo[cd]indol-4-amine (89)	240	C₁₆H₂₀N₂	Mutant strain cultured	[64]
(E)-N-Methyl-2-(4-(3-methylbuta-1,3-dien-1-yl)-1H-indol-3-yl)ethan-1-amine (90)	240	C₁₆H₂₀N₂	Mutant strain cultured	[64]
3,3′-Diindolylmethane (91)	246	C₁₇H₃₀N₂O₃	Deep-sea sediment, South China Sea	[31]
Terrequinone A (92)	490	C₃₂H₃₀N₂O₃	Deep-sea sediment, South China Sea	[31]
19-Hydroxypenitrem A (93)	649	C₃₇H₄₄ClNO₇	Polysiphonia scopulorum var. villum (Red alga, Rhodomelaceae), Yantai, North China	[38]
19-Hydroxypenitrem E (94)	615	C₃₇H₄₅NO₇	Polysiphonia scopulorum var. villum (Red alga, Rhodomelaceae), Yantai, North China	[38]
Penitrem A (95)	649	C₃₇H₄₄ClNO₇	Polysiphonia scopulorum var. villum (Red alga, Rhodomelaceae), Yantai, North China	[38]
Penijanthine A (96)	419	C₂₇H₃₃NO₃	Polysiphonia scopulorum var. villum (Red alga, Rhodomelaceae), Yantai, North China	[38]
Emindole DA (97)	405	C₂₈H₃₉NO	Green alga, Sardinia, Italy, Mediterranean Sea	[43]
Isoindole alkaloids
Cichorine (98)	193	C₁₀H₁₁NO₃	Cultured	[44,57]
Aspernidine A (99)	399	C₂₄H₃₃NO₄	Cultured	[65]
Aspernidine B (100)	385	C₂₃H₃₁NO₄	Cultured	[65]
Aspernidine C (101)	413	C₂₅H₃₅NO₄	Cultured	[49]
Aspernidine F (102)	443	C₂₆H₃₇NO₅	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China	[33]
Aspernidine G (103)	413	C₂₄H₃₁NO₅	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China	[33]
Aspernidine H (104)	457	C₂₆H₃₅NO₆	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China	[33]
Emericellolide A (105)	559	C₃₀H₄₁NO₉	Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China	[39]
Emericellolide B (106)	559	C₃₀H₄₁NO₉	Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China	[39]
Emericellolide C (107)	545	C₂₉H₃₉NO₉	Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China	[39]
Emeriphenolicin E (108)	733	C₄₄H₆₃NO₈	Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China	[39]
Emeriphenolicin F (109)	733	C₄₄H₆₃NO₈	Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China	[39]
Emeriphenolicin G (110)	747	C₄₅H₆₅NO₈	Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China	[39]

* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.

Table 8

Other nitrogenous compounds reported from A. nidulans.

Compound Name	Mol. Wt. *	Mol. Formula *	Host (Part, Family)/Location	Ref.
3′- Deoxyadenosine (111)	251	C₁₀H₁₃N₅O₃	Cultured	[67]
	-	-	Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt	[47]
Emerin (112)	316	C₂₀H₁₆N₂O₂	Cultured	[48]
Flavuside B (113)	755	C₄₃H₈₁N₇O₉	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]

* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.

Table 9

Peptides reported from A. nidulans.

Compound Name	Mol. Wt.	Mol. Formula	Host (Part, Family)	Ref.
Nidulanin A (114)	603	C₃₄H₄₅N₅O₅	Cultured	[56]
Echinocandin B (115)	1059	C₅₂H₈₁N₇O₁₆	Cultured	[70]
Aspercryptin A1 (116)	757	C₃₇H₇₁N₇O₉	Mutant strain cultured	[69]
Aspercryptin A2 (117)	741	C₃₇H₇₁N₇O₈	Mutant strain cultured	[69]
epi-Aspercryptin A2 (118)	741	C₃₇H₇₁N₇O₈	Mutant strain cultured	[69]
Aspercryptin A3 (119)	743	C₃₆H₆₉N₇O₉	Mutant strain cultured	[69]
Aspercryptin A4 (120)	729	C₃₅H₆₇N₇O₉	Mutant strain cultured	[69]
Aspercryptin A5 (121)	727	C₃₆H₆₉N₇O₈	Mutant strain cultured	[69]
Aspercryptin A6 (122)	713	C₃₅H₆₇N₇O₈	Mutant strain cultured	[69]
Aspercryptin A7 (123)	670	C₃₄H₆₆N₆O₇	Mutant strain cultured	[69]
Aspercryptin B1 (124)	933	C₄₇H₇₉N₇O₁₂	Mutant strain cultured	[69]
Aspercryptin B2 (125)	917	C₄₇H₇₉N₇O₁₁	Mutant strain cultured	[69]
Aspercryptin B3 (126)	919	C₄₆H₇₇N₇O₁₂	Mutant strain cultured	[69]
Aspercryptin B4 (127)	905	C₄₅H₇₅N₇O₁₂	Mutant strain cultured	[69]
Aspercryptin C1 (128)	799	C₃₉H₇₃N₇O₁₀	Mutant strain cultured	[69]
Aspercryptin C2 (129)	783	C₃₉H₇₃N₇O₉	Mutant strain cultured	[69]
Aspercryptin C3 (130)	785	C₃₈H₇₁N₇O₁₀	Mutant strain cultured	[69]
Aspercryptin C4 (131)	771	C₃₇H₆₉N₇O₁₀	Mutant strain cultured	[69]
Aspercryptin C6 (132)	755	C₃₇H₆₉N₇O₉	Mutant strain cultured	[69]
Aspercryptin D1 (133)	813	C₄₀H₇₅N₇O₁₀	Mutant strain cultured	[69]

Table 10

Terpenes reported from A. nidulans.

Compound Name	Mol. Wt.	Mol. Formula	Host (Part, Family)/Location	Ref.
ent-Pimara-8(14),15-diene (134)	272	C₂₀H₃₂	Engineered cultured	[71]
Neoaustinone (135)	442	C₂₅H₃₀O₇	Cultured	[56]
Niduterpenoid A (136)	404	C₂₅H₄₀O₄	Whitmania pigra Whitman (Annelida, segmented worm, Hirudinidae), Hubei, China	[40]
Niduterpenoid B (137)	404	C₂₅H₄₀O₄	Whitmania pigra Whitman (Annelida, segmented worm, Hirudinidae), Hubei, China	[40]
Austin (138)	500	C₂₇H₃₂O₉	Cultured	[72]
Dehydroaustin (139)	498	C₂₇H₃₀O₉	Cultured	[72]
Acetoxydehydroaustin (140)	556	C₂₉H₃₂O₁₁	Cultured	[72]
Austinolide (141)	442	C₂₅H₃₀O₇	Cultured	[56]
Austinol (142)	458	C₂₅H₃₀O₈	Cultured	[44,49,72]
	-	-	Deep-sea sediment, South China Sea	[31]
Dehydroaustinol (143)	456	C₂₅H₂₈O₈	Cultured	[44,49,72]
	-	-	Deep-sea sediment, South China Sea	[31]
β-Amyrin (144)	426	C₃₀H₅₀O	Cultured	[73]

Table 11

Sterols reported from A. nidulans.

Compound Name	Mol. Wt.	Mol. Formula	Host (Part, Family)/Location	Ref.
(7Z,9Z,17Z)-,2α,3β-Dihydroxypregna-7,9,17(20)-trien-18-al (145)	328	C₂₁H₂₈O₃	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China	[41]
Ergosterol (146)	396	C₂₈H₄₄O	Cultured	[41,74]
	-	-	Deep-sea sediment of the western Pacific Ocean, China	[58]
	-	-	Nyctanthes arbor-tristis (Oleaceae), Sabira	[53]
	-	-	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]
Lanosterol (147)	426	C₃₀H₅₀O	Cultured	[74]
Nidulanoid A (148)	486	C₃₀H₄₆O₅	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China	[41]
Nidulanoid B (149)	456	C₃₀H₄₈O₃	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China	[41]
(17E,22E,24R)-3β,5α-Dihydroxyergosta-7,17,22-trien-6,16-dione (150)	440	C₂₈H₄₀O₄	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China	[41]
Poriferastane-3β,6α-diol (151)	432	C₂₉H₅₂O₂	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China	[41]
3β,5α-Dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (152)	428	C₂₈H₄₄O₃	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China	[41]
(22E,24R)-Ergosta-7,22-dien-3β,5α,6α-triol (153)	430	C₂₈H₄₆O₃	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China	[41]
5α,8α-Epidoxyergosta-6,22-dien-3β-ol (154)	428	C₂₈H₄₄O₃	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China	[41]
	-	-	Deep-sea sediment, western Pacific Ocean, China	[58]
5α,8α-Epidioxyergosta-6,9(11),22-trien-3β-ol (155)	426	C₂₈H₄₂O₃	Deep-sea sediment, western Pacific Ocean, China	[58]
	-	-	Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt	[47]
(22E)-3β,4β,5α-Trihydroxyergosta-7,22-dien-6-one (156)	444	C₂₈H₄₄O₄	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China	[41]
5α,6α-Epoxy-3β-hydroxy-(22E)-ergosta-8(14),22-dien-7-one (157)	426	C₂₈H₄₂O₃	Deep-sea sediment, western Pacific Ocean, China	[58]
3β,5α,9α-Trihydroxyergosta-7,22-diene-6-one (158)	444	C₂₈H₄₄O₄	Deep-sea sediment, western Pacific Ocean, China	[58]
3β,5α-Dihydroxy-6β-acetoxy-ergosta-7,22-diene (159)	458	C₃₀H₅₀O₃	Deep-sea sediment, western Pacific Ocean, China	[58]
3β,5α,6β,22E-Ergosta-7,22-diene-3,5,6-triol 6-palmitate (160)	668	C₄₄H₇₆O₄	Deep-sea sediment, western Pacific Ocean, China	[58]
Nuatigenin (161)	430	C₂₇H₄₂O₄	Deep-sea sediment, western Pacific Ocean, China	[58]
1-Dehydronuatigenone (162)	426	C₂₇H₃₈O₄	Deep-sea sediment, western Pacific Ocean, China	[58]
1-Dehydroisonuatigenone (163)	426	C₂₇H₃₈O₄	Deep-sea sediment, western Pacific Ocean, China	[58]
3β,15α-Dihydroxyl-(22E,24R)-ergosta-5,8(14),22-trien-7-one (164)	426	C₂₈H₄₂O₃	Deep-sea sediment, western Pacific Ocean, China	[58]
3β,15β-Dihydroxyl-(22E,24R)-ergosta-5,8(14),22-trien-7-one (165)	426	C₂₈H₄₂O₃	Deep-sea sediment, western Pacific Ocean, China	[58]
β-Sitosterol-3-O-β-D-glucoside (166)	576	C₃₅H₆₀O₆	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]
Ergosterol peroxide (167)	428	C₂₈H₄₄O₃	Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt	[47]

Table 12

Furan and pyran derivatives reported from A. nidulans.

Compound Name	Mol. Wt.	Mol. Formula	Host (Part, Family)	Ref.
Nidulol (168)	194	C₁₀H₁₀O₄	Cultured	[51]
Porriolide (169)	194	C₁₀H₁₀O₄	Cultured	[57]
3-Methoxyporriolide (170)	224	C₁₁H₁₂O₅	Cultured	[57]
7-Methoxyporriolide (171)	224	C₁₁H₁₂O₅	Cultured	[57]
3-Carboxy-2,4-diphenyl-but-2-enoic anhydride (172)	264	C₁₇H₁₂O₃	Cultured	[75]
Microperfuranone (173)	266	C₁₇H₁₄O₃	Green alga, Sardinia, Italy, Mediterranean Sea	[43]
	-	-	Soil, Hell Valley, Noboribetsu, Hokkaido, Japan	[52]
	-	-	Cultured	[57]
	-	-	Deep-sea sediment, South China Sea	[31]
9-Hydroxymicroperfuranone (174)	282	C₁₇H₁₄O₄	Soil, Hell Valley, Noboribetsu, Hokkaido, Japan	[52]
9-Hydroxymicroperfuranone (174)	-	-	Deep-sea sediment, South China Sea	[31]
Helvafuranone (175)	298	C₁₇H₁₄O₅	Soil, Hell Valley, Noboribetsu, Hokkaido, Japan	[52]
Asperfuranone (176)	332	C₁₉H₂₄O₅	Mutant strain cultured	[76]
Cichorine intermediate (177)	196	C₁₀H₁₂O₄	Cultured	[56]
(4S,5R)-4-Hydroxy-5-methylfuran-2-one (178)	132	C₅H₈O₄	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]
Asperlin (U-13,933) (179)	212	C₁₀H₁₂O₅	Cultured	[75,77,78]
Chloro-asperlin (180)	248	C₁₀H₁₃ClO₅	Cultured	[77]
Versiol (181)	262	C₁₆H₂₂O₃	Deep-sea sediment, western Pacific Ocean, China	[58]
PsiAα (182)	294	C₁₈H₃₀O₃	Cultured	[79]
PsiAβ (183)	296	C₁₈H₃₂O₃	Cultured	[79]
Trichodermatide B (184)	264	C₁₆H₂₄O₃	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]
Koninginin A (185)	284	C₁₆H₂₈O₄	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]
Koninginin E (186)	282	C₁₆H₂₆O₄	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]
Koninginin H (187)	298	C₁₆H₂₆O₅	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]
Asperlinol (188)	230	C₁₀H₁₄O₆	Cultured	[77]

Table 13

Polyketides and glycerides reported from A. nidulans.

Compound Name/Chemical Class	Mol. Wt.	Mol. Formula	Host (Part, Family)	Ref.
Polyketides
Curvularin (189)	292	C₁₆H₂₀O₅	Deep-sea sediment, South China Sea	[31]
Emerione A (190)	472	C₂₉H₄₄O₅	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China	[80]
Emerione B (191)	472	C₂₉H₄₄O₅	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China	[80]
Emerione C (192)	488	C₂₉H₄₄O₆	Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China	[80]
Citrantifidiol (193)	240	C₁₅H₂₈O₂	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]
Glycerides
Gingerglycolipid B (194)	678	C₃₃H₅₈O₁₄	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]
(2S)-bis[9Z,12Z]-1-O, 2- O-Dilinoleoyl-3-O-[α-D-galactopyranosyl-(1″→6′) β-D-galactopyranosyl]glycerol (195)	940	C₅₁H₈₈O₁₅	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]
(2S)-bis[9Z,12Z]-1-O, 2-O-dilinoleoyl-3-O-β-D-galactopyranosylglycerol (196)	778	C₄₅H₇₈O₁₀	Piece of orange peel (Rutaceae), Tifton, Georgia	[68]

Table 14

Other metabolites reported from A. nidulans.

Compound Name	Mol. Wt.	Mol. Formula	Host (Part, Family)	Ref.
Aspernidine D (197)	386	C₂₄H₃₄O₄	Cultured	[49]
Aspernidine E (198)	402	C₂₄H₃₄O₅	Cultured	[49]
Asperbenzaldehyde (199)	316	C₁₉H₂₄O₄	Cultured	[54]
3-Methylorsellinic acid (200)	182	C₉H₁₀O₄	Cultured	[56]
O-Methyl-3-methylorsellinaldehyde dimer (201)	360	C₂₀H₂₄O₆	Cultured	[56]
6-((S,3E,5E)-5,7-Dimethyl-2-oxonona-3,5-dien-1-yl)-2,4-dihydroxy- 3-methylbenzaldehyde (202)	316	C₁₉H₂₄O₄	Mutant strain cultured	[42]
Lecanoric acid (203)	318	C₁₆H₁₄O₇	Deep-sea sediment, South China Sea	[31]
Myristic acid (204)	228	C₁₄H₂₈O₂	Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt	[47]
Atrochrysone (205)	274	C₁₅H₁₄O₅	Cultured	[56]
Asperoxide A (206)	234	C₁₂H₂₆O₄	Deep-sea sediment, South China Sea	[31]

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Nowadays, finding out new natural scaffolds of microbial origin increases at a higher rate than in the past decades and represents an auspicious route for reinvigorating the pool of compounds entering pharmaceutical industries. Fungi serve as a depository of fascinating, structurally unique metabolites with considerable therapeutic significance. Aspergillus genus represents one of the most prolific genera of filamentous fungi. Aspergillus nidulans Winter G. is a well-known and plentiful source of bioactive metabolites with abundant structural diversity, including terpenoids, benzophenones, sterols, alkaloids, xanthones, and polyketides, many of which display various bioactivities, such as cytotoxicity, antioxidant, anti-inflammatory, antiviral, and antimicrobial activities. The current work is targeted to survey the reported literature on A. nidulans, particularly its metabolites, biosynthesis, and bioactivities, in addition to recent reports on its biotechnological potential. From 1953 till November 2022, relying on the stated data, 206 metabolites were listed, with more than 100 references.

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Title

Aspergillus nidulans—Natural Metabolites Powerhouse: Structures, Biosynthesis, Bioactivities, and Biotechnological Potential

Author

Ghazawi, Kholoud F¹; Fatani, Sarah A²; Mohamed, Shaimaa G A³; Mohamed, Gamal A⁴

; Ibrahim, Sabrin R M⁵

¹ Clinical Pharmacy Department, College of Pharmacy, Umm Al-Qura University, Makkah 24382, Saudi Arabia; [email protected]
² Department of Clinical Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
³ Faculty of Dentistry, British University, El Sherouk City, Suez Desert Road, Cairo 11837, Egypt; [email protected]
⁴ Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
⁵ Preparatory Year Program, Department of Chemistry, Batterjee Medical College, Jeddah 21442, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt

First page

325

Publication year

2023

Publication date

2023

Publisher

MDPI AG

e-ISSN

23115637

Source type

Scholarly Journal

Language of publication

English

DOI

https://doi.org/10.3390/fermentation9040325

ProQuest document ID

2806532811

Aspergillus nidulans—Natural Metabolites Powerhouse: Structures, Biosynthesis, Bioactivities, and Biotechnological Potential

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