Fungal ribosomally synthesized and post-translationally modified peptides (RiPPs) are a vital class of natural products known for their biological activities including anticancer, antitubulin, antinematode, and immunosuppressant properties. These bioactive fungal RiPPs play key roles in chemical ecology and have a significant therapeutic potential. Their structural diversity, which arises from intricate post-translational modifications of precursor peptides, is particularly remarkable. Despite their biological and ecological importance, the discovery of fungal RiPPs has been historically challenging and only a limited number have been identified. To date, known fungal RiPPs are primarily grouped into three groups: cycloamanides and borosins from basidiomycetes and dikaritins from ascomycetes. Recent advancements in bioinformatics have revealed the vast untapped potential of fungi to produce RiPPs, offering new opportunities for their discovery. This review highlights recent progress in fungal RiPP biosynthesis and genome-guided discovery strategies. We propose that combining the knowledge of fungal RiPP biosynthetic pathways with advanced gene-editing technologies and bioinformatic tools will significantly accelerate the discovery of novel bioactive fungal RiPPs.
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http://dx.doi.org/10.1021/acs.biochem.4c00532 | DOI Listing |
Org Biomol Chem
November 2024
Centre Algatech, Institute of Microbiology, Czech Academy of Sciences, Novohradká 237, Centre Algatech, Institute of Microbiology, Czech Academy of Sciences, 379 01 Třeboň, Czech Republic.
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are intriguing compounds with potential pharmacological applications. While many RiPPs are known as antimicrobial agents, a limited number of RiPPs with anti-proliferative effects in cancer cells are available. Here we report the discovery of nostatin A (NosA), a highly modified RiPP belonging among nitrile hydratase-like leader peptide RiPPs (proteusins), isolated from a terrestrial cyanobacterium sp.
View Article and Find Full Text PDFACS Infect Dis
November 2024
Center for Sustainable Antimicrobials, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
The rapid emergence of antibiotic-resistant strains of presents a substantial challenge to global public health, underscoring the urgent need for novel antibiotics with diverse mechanisms of action. In this study, we conducted mutagenesis on the -terminal region of the lantibiotic ripcin C to enhance its antimicrobial efficacy against . The resulting optimized variant, ripcin C, demonstrated potent and selective antimicrobial activity, with a minimal inhibitory concentration of 2-4 mg/L against .
View Article and Find Full Text PDFBiochemistry
November 2024
Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Chem
October 2024
Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Vladimir-Prelog Weg 4, 8093 Zürich, Switzerland.
Isoprenoid modifications of proteins and peptides serve fundamental biological functions and are of therapeutic interest. While C (farnesyl) and C (geranylgeranyl) moieties are prevalent among proteins, known ribosomal peptide prenylations involve shorter-chain units not exceeding farnesyl in size. To our knowledge, cyclized terpene moieties have not been reported from either biomolecule class.
View Article and Find Full Text PDFCurr Issues Mol Biol
August 2024
Department of Biochemistry and Microbiology, Faculty of Biology, University of Plovdiv, Tzar Assen 24, 4000 Plovdiv, Bulgaria.
The genus is renowned not only for its natural antibiotic production but also for its abundant chitinolytic enzymes, which break down stubborn chitin into chitooligosaccharides. Despite this, there have been limited studies utilizing whole-genome sequencing to explore the repertoire of chitin degradation and utilization genes in . A particularly compelling source of novel antimicrobials and enzymes lies in the microbiota of insects, where bacterial symbionts produce antimicrobials to protect against opportunistic pathogens and enzymes to adapt to the environment.
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