Dataset Information

A Review of Fungal Protoilludane Sesquiterpenoid Natural Products.

ABSTRACT: Natural products have been a great source for drug leads, due to a vast majority possessing unique chemical structures. Such an example is the protoilludane class of natural products which contain an annulated 5/6/4-ring system and are almost exclusively produced by fungi. They have been reported to possess a diverse range of bioactivities, including antimicrobial, antifungal and cytotoxic properties. In this review, we discuss the isolation, structure elucidation and any reported bioactivities of this compound class, including establishment of stereochemistry and any total syntheses of these natural products. A total of 180 protoilludane natural products, isolated in the last 70 years, from fungi, plant and marine sources are covered, highlighting their structural diversity and potential in drug discovery.

SUBMITTER: Cadelis MM

PROVIDER: S-EPMC7765842 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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A Review of Fungal Protoilludane Sesquiterpenoid Natural Products.

Cadelis Melissa M MM Copp Brent R BR Wiles Siouxsie S

Antibiotics (Basel, Switzerland) 20201219 12

Natural products have been a great source for drug leads, due to a vast majority possessing unique chemical structures. Such an example is the protoilludane class of natural products which contain an annulated 5/6/4-ring system and are almost exclusively produced by fungi. They have been reported to possess a diverse range of bioactivities, including antimicrobial, antifungal and cytotoxic properties. In this review, we discuss the isolation, structure elucidation and any reported bioactivities ...[more]

PMID: 33352728

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Project description:The pool of fungal secondary metabolites can be extended by activating silent gene clusters of cultured strains or by using sensitive biological assays that detect metabolites missed by analytical methods. Alternatively, or in parallel with the first approach, one can increase the diversity of existing culture collections to improve the access to new natural products. This review focuses on the latter approach of screening previously uncultured fungi for chemodiversity. Both strategies have been practiced since the early days of fungal biodiscovery, yet relatively little has been done to overcome the challenge of cultivability of as-yet-uncultivated fungi. Whereas earlier cultivability studies using media formulations and biological assays to scrutinize fungal growth and associated factors were actively conducted, the application of modern omics methods remains limited to test how to culture the fungal dark matter and recalcitrant groups of described fungi. This review discusses the development of techniques to increase the cultivability of filamentous fungi that include culture media formulations and the utilization of known chemical growth factors, in situ culturing and current synthetic biology approaches that build upon knowledge from sequenced genomes. We list more than 100 growth factors, i.e., molecules, biological or physical factors that have been demonstrated to induce spore germination as well as tens of inducers of mycelial growth. We review culturing conditions that can be successfully manipulated for growth of fungi and visit recent information from omics methods to discuss the metabolic basis of cultivability. Earlier work has demonstrated the power of co-culturing fungi with their host, other microorganisms or their exudates to increase their cultivability. Co-culturing of two or more organisms is also a strategy used today for increasing cultivability. However, fungi possess an increased risk for cross-contaminations between isolates in existing in situ or microfluidics culturing devices. Technological improvements for culturing fungi are discussed in the review. We emphasize that improving the cultivability of fungi remains a relevant strategy in drug discovery and underline the importance of ecological and taxonomic knowledge in culture-dependent drug discovery. Combining traditional and omics techniques such as single cell or metagenome sequencing opens up a new era in the study of growth factors of hundreds of thousands of fungal species with high drug discovery potential.

Project description:Microorganisms produce a wide range of natural products (NPs) with clinically and agriculturally relevant biological activities. In bacteria and fungi, genes encoding successive steps in a biosynthetic pathway tend to be clustered on the chromosome as biosynthetic gene clusters (BGCs). Historically, "activity-guided" approaches to NP discovery have focused on bioactivity screening of NPs produced by culturable microbes. In contrast, recent "genome mining" approaches first identify candidate BGCs, express these biosynthetic genes using synthetic biology methods, and finally test for the production of NPs. Fungal genome mining efforts and the exploration of novel sequence and NP space are limited, however, by the lack of a comprehensive catalog of BGCs encoding experimentally-validated products. In this study, we generated a comprehensive reference set of fungal NPs whose biosynthetic gene clusters are described in the published literature. To generate this dataset, we first identified NCBI records that included both a peer-reviewed article and an associated nucleotide record. We filtered these records by text and homology criteria to identify putative NP-related articles and BGCs. Next, we manually curated the resulting articles, chemical structures, and protein sequences. The resulting catalog contains 197 unique NP compounds covering several major classes of fungal NPs, including polyketides, non-ribosomal peptides, terpenoids, and alkaloids. The distribution of articles published per compound shows a bias toward the study of certain popular compounds, such as the aflatoxins. Phylogenetic analysis of biosynthetic genes suggests that much chemical and enzymatic diversity remains to be discovered in fungi. Our catalog was incorporated into the recently launched Minimum Information about Biosynthetic Gene cluster (MIBiG) repository to create the largest known set of fungal BGCs and associated NPs, a resource that we anticipate will guide future genome mining and synthetic biology efforts toward discovering novel fungal enzymes and metabolites.

Dataset Information

A Review of Fungal Protoilludane Sesquiterpenoid Natural Products.

Publications

A Review of Fungal Protoilludane Sesquiterpenoid Natural Products.

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