Abstract
Ribosomally synthesized and post-translationally modified peptides (RiPPs) form a highly diverse class of natural products, with various biotechnologically and clinically relevant activities. A recent increase in discoveries of novel RiPP classes suggests that currently known RiPPs constitute just the tip of the iceberg. Genome mining has been a driving force behind these discoveries, but remains challenging due to a lack of universal genetic markers for RiPP detection. In this review, we discuss how various genome mining methodologies contribute towards the discovery of novel RiPP classes. Some methods prioritize novel biosynthetic gene clusters (BGCs) based on shared modifications between RiPP classes. Other methods identify RiPP precursors using machine-learning classifiers. The integration of such methods as well as integration with other types of omics data in more comprehensive pipelines could help these tools reach their potential, and keep pushing the boundaries of the chemical diversity of this important class of molecules.
Highlights
Small organic molecules from a biological origin, collectively called natural products, comprise a dazzling array of diverse chemical structures [1]
Bioactive natural products find their way into the clinic, as a result of their antimicrobial, antifungal, The biosynthesis of natural products typically requires a distinct set of conserved enzymes that is responsible for their biosynthesis
ribosomally synthesized and post-translationally modified peptides (RiPPs) biosynthesis always follows the same logic—a precursor peptide is ribosomally synthesized, biochemically modified and cleaved, resulting in the finished product (Figure 1)—but numerous different precursors and sets of modifying enzymes acting on them leads to large structural diversity (Figure 2)
Summary
Small organic molecules from a biological origin, collectively called natural products, comprise a dazzling array of diverse chemical structures [1]. RiPP biosynthesis always follows the same logic—a precursor peptide is ribosomally synthesized, biochemically modified and cleaved, resulting in the finished product (Figure 1)—but numerous different precursors and sets of modifying enzymes acting on them leads to large structural diversity (Figure 2). Their functions are diverse, and Current Opinion in Biotechnology 2021, 69:60–67 www.sciencedirect.com. Taking the bait: how to prioritize regions of interest Marker-based genome mining has been the main strategy for the high-confidence detection of BGCs from known classes of RiPPs. For many RiPP classes, modifying enzymes are split into core and accessory types, depending on the type of modification installed. For the detection of novel RiPP classes, www.sciencedirect.com
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