Exploring Bioactive Fungal RiPPs: Advances, Challenges, and Future Prospects.

Biochemistry

Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

Published: November 2024

AI Article Synopsis

  • Fungal ribosomally synthesized and post-translationally modified peptides (RiPPs) are important natural products with various biological activities such as anticancer and immunosuppressive effects.
  • Despite their significance, discovering these compounds has been difficult, leading to only a few identified types that primarily include cycloamanides, borosins, and dikaritins.
  • Recent advancements in bioinformatics and genome-guided discovery methods promise to enhance the identification of novel bioactive fungal RiPPs by integrating knowledge of biosynthetic pathways with gene-editing technologies.

Article Abstract

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.4c00532DOI Listing

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