https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

This review presents an update on the current knowledge of the secondary metabolite potential of the major fungal species used in industrial biotechnology, i.e., Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei. These species have a long history of safe use for enzyme production. Like most microorganisms that exist in a challenging environment in nature, these fungi can produce a large variety and number of secondary metabolites. Many of these compounds present several properties that make them attractive for different industrial and medical applications. A description of all known secondary metabolites produced by these species is presented here. Mycotoxins are a very limited group of secondary metabolites that can be produced by fungi and that pose health hazards in humans and other vertebrates when ingested in small amounts. Some mycotoxins are species-specific. Here, we present scientific basis for (1) the definition of mycotoxins including an update on their toxicity and (2) the clarity on misclassification of species and their mycotoxin potential reported in literature, e.g., A. oryzae has been wrongly reported as an aflatoxin producer, due to misclassification of Aspergillus flavus strains. It is therefore of paramount importance to accurately describe the mycotoxins that can potentially be produced by a fungal species that is to be used as a production organism and to ensure that production strains are not capable of producing mycotoxins during enzyme production. This review is intended as a reference paper for authorities, companies, and researchers dealing with secondary metabolite assessment, risk evaluation for food or feed enzyme production, or considerations on the use of these species as production hosts.

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Safety of the fungal workhorses of industrial biotechnology: update on the mycotoxin and secondary metabolite potential of Aspergillus niger , Aspergillus oryzae , and Trichoderma reesei

The inherent modularity of polypeptides, oligonucleotides and oligosaccharides has been harnessed to achieve generalized synthesis platforms. Importantly, like these other targets, most small-molecule natural products are biosynthesized via iterative coupling of bifunctional building blocks. This suggests that many small molecules also possess inherent modularity commensurate with systematic building block-based construction. Supporting this hypothesis, here we report that the polyene motifs found in >75% of all known polyene natural products can be synthesized using just 12 building blocks and one coupling reaction. Using the same general retrosynthetic algorithm and reaction conditions, this platform enabled both the synthesis of a wide range of polyene frameworks that covered all of this natural-product chemical space and the first total syntheses of the polyene natural products asnipyrone B, physarigin A and neurosporaxanthin b-D-glucopyranoside. Collectively, these results suggest the potential for a more generalized approach to making small molecules in the laboratory.

/pdf/synthesis-of-most-polyene-natural-product-motifs-using-just-2h6twd3ibq.pdf

Synthesis of most polyene natural product motifs using just 12 building blocks and one coupling reaction

Metabolites from marine fungi have hogged the limelight in drug discovery because of their promise as therapeutic agents. A number of metabolites related to marine fungi have been discovered from various sources which are known to possess a range of activities as antibacterial, antiviral and anticancer agents. Although, over a thousand marine fungi based metabolites have already been reported, none of them have reached the market yet which could partly be related to non-comprehensive screening approaches and lack of sustained lead optimization. The origin of these marine fungal metabolites is varied as their habitats have been reported from various sources such as sponge, algae, mangrove derived fungi, and fungi from bottom sediments. The importance of these natural compounds is based on their cytotoxicity and related activities that emanate from the diversity in their chemical structures and functional groups present on them. This review covers the majority of anticancer compounds isolated from marine fungi during 2012-2016 against specific cancer cell lines.

/pdf/marine-fungi-a-source-of-potential-anticancer-compounds-200jd07nff.pdf

Marine Fungi: A Source of Potential Anticancer Compounds.

This paper reviews 116 new compounds with antifungal or antibacterial activities as well as 169 other known antimicrobial compounds, with a specific focus on January 2010 through March 2015 Furthermore, the phylogeny of the fungi producing these antibacterial or antifungal compounds was analyzed The new methods used to isolate marine fungi that possess antibacterial or antifungal activities as well as the relationship between structure and activity are shown in this review

Antibacterial and Antifungal Compounds from Marine Fungi

Eight new a-pyrone derivatives, namely, nigerapyrones A-E (1-5) and nigerapyrones F-H (8-10), along with two known congeners, asnipyrones B (6) and A (7), were isolated from Aspergillus niger MA-132, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Avicennia marina. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The undescribed geometries of the trisubstituted double bonds (C-9 and C-11) for asnipyrone B (6) have now been explicitly determined, while the incorrect placement of the methyl group at C-5 of asnipyrone A (7) has now been revised at C-3. The cytotoxic activities of the isolated a-pyrone derivatives against eight tumor cell lines as well as antimicrobial activities against two bacteria and four plant-pathogenic fungi of these compounds were evaluated. Compounds 2, 4, 5, and 7 showed weak cytotoxicity against some of the tested tumor cell lines.

Nigerapyrones A-H, α-pyrone derivatives from the marine mangrove-derived endophytic fungus Aspergillus niger MA-132.

Two new 6,8(14),22-hexadehydro-5,9-epidioxy-3,15-dihydroxy sterols, nigerasterols A and B (1 and 2, resp.), together with two known cyclopentapeptides, malformins A1 and C (3 and 4, resp.), were identified in the culture extract of Aspergillus niger MA-132, an endophytic fungus isolated from a fresh healthy sample of the mangrove plant Avicennia marina. The structures and relative configurations of these compounds were established on the basis of extensive spectroscopic analyses. The absolute configuration of compound 1 was determined by application of a modified version of Mosher's method. Nigerasterols A and B (1 and 2, resp.) represent the first 5,9-epidioxy-sterol compounds of marine origin, and they displayed potent activity against tumor cell lines HL60 and A549 in a preliminary bioassay.

Nigerasterols A and B, Antiproliferative Sterols from the Mangrove-Derived Endophytic Fungus Aspergillus niger MA-132

Two new tricyclic sesterterpenes, fusaprolifins A and B (1 and 2), and three new 2H-pyran-2-one derivatives, prolipyrones A C (35), were isolated and characterized from Fusarium proliferatum MA-84, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Bruguiera sexangula. In addition, two known sesterterpenes, terpestacin (6) and fusaproliferin (7), and one known 2H-pyran-2-one derivative, gibepyrone D (8), were also identified. The structures of these compounds were elucidated by detailed spectroscopic analyses. Fusaprolifin A (1) showed moderate activity against brine shrimp (Artemia salina), with a lethality rate of 49.5% at 100g/ml, while fusaprolifin B (2) showed weak activity.

Dong Liu

Papers

Nigerapyrones A-H, α-pyrone derivatives from the marine mangrove-derived endophytic fungus Aspergillus niger MA-132.

Nigerasterols A and B, Antiproliferative Sterols from the Mangrove-Derived Endophytic Fungus Aspergillus niger MA-132

Sesterterpenes and 2H-Pyran-2-ones (=alpha-Pyrones) from the Mangrove-Derived Endophytic Fungus Fusarium proliferatum MA-84