Abstract
BackgroundRibosomally synthesized and post-translationally modified peptides (RiPPs) are a highly diverse group of secondary metabolites (SM) of bacterial and fungal origin. While RiPPs have been intensively studied in bacteria, little is known about fungal RiPPs. In Fungi only six classes of RiPPs are described. Current strategies for genome mining are based on these six known classes. However, the genes involved in the biosynthesis of theses RiPPs are normally organized in biosynthetic gene clusters (BGC) in fungi.ResultsHere we describe a comprehensive strategy to mine fungal genomes for RiPPs by combining and adapting existing tools (e.g. antiSMASH and RiPPMiner) followed by extensive manual curation based on conserved domain identification, (comparative) phylogenetic analysis, and RNASeq data. Deploying this strategy, we could successfully rediscover already known fungal RiPPs. Further, we analysed four fungal genomes from the Trichoderma genus. We were able to find novel potential RiPP BGCs in Trichoderma using our unconventional mining approach.ConclusionWe demonstrate that the unusual mining approach using tools developed for bacteria can be used in fungi, when carefully curated. Our study is the first report of the potential of Trichoderma to produce RiPPs, the detected clusters encode novel uncharacterized RiPPs. The method described in our study will lead to further mining efforts in all subdivisions of the fungal kingdom.
Highlights
Synthesized and post-translationally modified peptides (RiPPs) are a highly diverse group of secondary metabolites (SM) of bacterial and fungal origin
We mined the genomes of A. flavus and Amanita phalloides in which fungal
These results demonstrate that the RiPPMiner software is able to identify fungal Ribosomally synthesized and post-translationally modified peptides (RiPPs) precursors, it was designed to predict bacterial RiPPs
Summary
Synthesized and post-translationally modified peptides (RiPPs) are a highly diverse group of secondary metabolites (SM) of bacterial and fungal origin. Secondary metabolites (SMs) from fungal sources have played a crucial role in improving human health since the discovery of Penicillin, but even in prehistoric times [1, 2]. These natural products and chemically modified variants are widely used as antibiotics, immunomodulators and anti-cancer drugs [3]. Wellknown examples of fungal SMs belong to two main classes They are either polyketides (e.g. the mycotoxin aflatoxin and the cholesterol-lowering drug lovastatin) or non-ribosomal peptides (e.g. the antibiotic penicillin and Institute of Chemical, Environmental and Bioscience Engineering, TU Wien, Gumpendorfer Strasse 1a, 1060 Wien, Austria the immunosuppressant cyclosporine). RiPPs are a rapid growing group of natural products that can be classified in more than 20 different compound classes
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