Cytochromes P450 involved in bacterial RiPP biosyntheses

J Ind Microbiol Biotechnol. 2023 Feb 17;50(1):kuad005. doi: 10.1093/jimb/kuad005.

Abstract

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a large class of secondary metabolites that have garnered scientific attention due to their complex scaffolds with potential roles in medicine, agriculture, and chemical ecology. RiPPs derive from the cleavage of ribosomally synthesized proteins and additional modifications, catalyzed by various enzymes to alter the peptide backbone or side chains. Of these enzymes, cytochromes P450 (P450s) are a superfamily of heme-thiolate proteins involved in many metabolic pathways, including RiPP biosyntheses. In this review, we focus our discussion on P450 involved in RiPP pathways and the unique chemical transformations they mediate. Previous studies have revealed a wealth of P450s distributed across all domains of life. While the number of characterized P450s involved in RiPP biosyntheses is relatively small, they catalyze various enzymatic reactions such as C-C or C-N bond formation. Formation of some RiPPs is catalyzed by more than one P450, enabling structural diversity. With the continuous improvement of the bioinformatic tools for RiPP prediction and advancement in synthetic biology techniques, it is expected that further cytochrome P450-mediated RiPP biosynthetic pathways will be discovered.

Summary: The presence of genes encoding P450s in gene clusters for ribosomally synthesized and post-translationally modified peptides expand structural and functional diversity of these secondary metabolites, and here, we review the current state of this knowledge.

Keywords: Cytochrome P450; Natural products; RiPP; Secondary metabolites.

Publication types

  • Review

MeSH terms

  • Bacteria / genetics
  • Bacteria / metabolism
  • Biological Products* / chemistry
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Peptides / metabolism
  • Protein Processing, Post-Translational
  • Ribosomes* / genetics
  • Ribosomes* / metabolism

Substances

  • Peptides
  • Cytochrome P-450 Enzyme System
  • Biological Products