1. Bacterial cyclophane-containing RiPPs from radical SAM enzymes.
- Author
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Phan, Chin-Soon and Morinaka, Brandon I.
- Subjects
- *
RADICALS (Chemistry) , *DRUG discovery , *ENZYMES , *PEPTIDES , *NATURAL products - Abstract
Covering: 2016 to 2023 Ribosomally synthesized and posttranslationally modified peptides (RiPPs) continue to be a rich source of chemically diverse and bioactive peptide natural products. In recent years, cyclophane-containing RiPP natural products and their biosynthetic pathways have been more frequently encountered. This highlight will focus on bacterial monoaryl cyclophane-containing RiPPs. This class of RiPPs is produced by radical SAM/SPASM enzymes that form a crosslink between the aromatic ring and sidechain of two amino acid residues of the precursor peptide. Selected natural products from these pathways exhibit specific antibacterial activity against gram-negative pathogens. The approaches used to discover these pathways and products will be described and categorized as natural product-first or enzyme-first. The breadth of ring systems formed by the enzymes, enzyme mechanism, and recent reports of synthetic methods for constructing these ring systems will also be presented. Bacterial cyclophane-containing RiPPs and their biosynthetic enzymes represent an untapped source of scaffolds for drug discovery and tools for synthetic biology. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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