Dataset Information

Dual-PKS Cluster for Biosynthesis of a Light-Induced Secondary Metabolite Found from Genome Sequencing of Hyphodiscus hymeniophilus Fungus.

ABSTRACT: Filamentous fungi are known producers of important secondary metabolites. In spite of this, the majority of these organisms have not been studied at the genome level, leaving many of the bioactive molecules they produce undiscovered. In this study, we explore the secondary metabolite potential of an understudied fungus, Hyphodiscus hymeniophilus. By sequencing and assembling the first genome from this genus, we show that this fungus has genes for at least 20 natural products and that many of these products are likely novel. One of these metabolites is identified: a new, red-pigmented member of the azaphilone class, hyphodiscorubrin. We show that this metabolite is only produced when the fungus is grown in the light. Furthermore, the biosynthetic gene cluster of hyphodiscorubrin is identified though homology to other known azaphilone producing clusters.

SUBMITTER: Kramer GJ

PROVIDER: S-EPMC7496686 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Dual-PKS Cluster for Biosynthesis of a Light-Induced Secondary Metabolite Found from Genome Sequencing of Hyphodiscus hymeniophilus Fungus.

Kramer Glenna J GJ Pimentel-Elardo Sheila S Nodwell Justin R JR

Chembiochem : a European journal of chemical biology 20200421 15

Filamentous fungi are known producers of important secondary metabolites. In spite of this, the majority of these organisms have not been studied at the genome level, leaving many of the bioactive molecules they produce undiscovered. In this study, we explore the secondary metabolite potential of an understudied fungus, Hyphodiscus hymeniophilus. By sequencing and assembling the first genome from this genus, we show that this fungus has genes for at least 20 natural products and that many of the ...[more]

PMID: 32314858

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Project description:Fungal secondary metabolites with antibiotic activities can promote fungal adaptation to diverse environments. Besides the global regulator, individual biosynthetic gene clusters (BGCs) usually contain a pathway-specific transcription factor for the tight regulation of fungal secondary metabolism. Here, we report the chemical biology mediated by a supercluster containing three BGCs in the entomopathogenic fungus Metarhizium robertsii. These clusters are jointly controlled by an embedded transcription factor that orchestrates the collective production of four classes of chemicals: ustilaginoidin, indigotide, pseurotin, and hydroxyl-ovalicin. The ustilaginoidin BGC is implicated as a late-acquired cluster in Metarhizium to produce both the bis-naphtho-γ-pyrones and the monomeric naphtho-γ-pyrone glycosides (i.e., indigotides). We found that the biosynthesis of indigotides additionally requires the functions of paired methylglucosylation genes located outside the supercluster. The pseurotin/ovalicin BGCs are blended and mesosyntenically conserved to the intertwined pseurotin/fumagillin BGCs of Aspergillus fumigatus. However, the former have lost a few genes, including a polyketide synthase gene responsible for the production of a pentaene chain used for assembly with ovalicin to form fumagillin, as observed in A. fumigatus. The collective production of chemical cocktails by this supercluster was dispensable for fungal virulence against insects and could enable the fungus to combat different bacteria better than the metabolite(s) produced by an individual BGC could. Thus, our results unveil a novel strategy employed by fungi to manage chemical ecology against diverse bacteria. IMPORTANCE Fungal chemical ecology is largely mediated by the metabolite(s) produced by individual biosynthetic gene clusters (BGCs) with antibiotic activities. We report a supercluster containing three BGCs that are jointly controlled by an embedded master regulator in the insect pathogen Metarhizium robertsii. Four classes of chemicals, namely, ustilaginoidin, indigotide, pseurotin, and hydroxyl-ovalicin, are collectively produced by these three BGCs along with the contributions of tailoring enzyme genes located outside the supercluster. The production of these metabolites is not required for the fungal infection of insect hosts, but it benefits the fungus to combat diverse bacteria. The findings reveal and advocate a "the-more-the-better" strategy employed by fungi to manage effective adaptations to diverse environments.

Project description:A diverse collection of 60 marine-sediment-derived Actinobacteria representing 52 operational taxonomic units was screened by PCR for genes associated with secondary-metabolite biosynthesis. Three primer sets were employed to specifically target adenylation domains associated with nonribosomal peptide synthetases (NRPSs) and ketosynthase (KS) domains associated with type I modular, iterative, hybrid, and enediyne polyketide synthases (PKSs). In total, two-thirds of the strains yielded a sequence-verified PCR product for at least one of these biosynthetic types. Genes associated with enediyne biosynthesis were detected in only two genera, while 88% of the ketosynthase sequences shared greatest homology with modular PKSs. Positive strains included representatives of families not traditionally associated with secondary-metabolite production, including the Corynebacteriaceae, Gordoniaceae, Intrasporangiaceae, and Micrococcaceae. In four of five cases where phylogenetic analyses of KS sequences revealed close evolutionary relationships to genes associated with experimentally characterized biosynthetic pathways, secondary-metabolite production was accurately predicted. Sequence clustering patterns were used to provide an estimate of PKS pathway diversity and to assess the biosynthetic richness of individual strains. The detection of highly similar KS sequences in distantly related strains provided evidence of horizontal gene transfer, while control experiments designed to amplify KS sequences from Salinispora arenicola strain CNS-205, for which a genome sequence is available, led to the detection of 70% of the targeted PKS pathways. The results provide a bioinformatic assessment of secondary-metabolite biosynthetic potential that can be applied in the absence of fully assembled pathways or genome sequences. The rapid identification of strains that possess the greatest potential to produce new secondary metabolites along with those that produce known compounds can be used to improve the process of natural-product discovery by providing a method to prioritize strains for fermentation studies and chemical analysis.

Dataset Information

Dual-PKS Cluster for Biosynthesis of a Light-Induced Secondary Metabolite Found from Genome Sequencing of Hyphodiscus hymeniophilus Fungus.

Publications

Dual-PKS Cluster for Biosynthesis of a Light-Induced Secondary Metabolite Found from Genome Sequencing of Hyphodiscus hymeniophilus Fungus.

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