Recent advances in thiopeptide antibiotic biosynthesis

Nat Prod Rep. 2010 Feb;27(2):153-64. doi: 10.1039/b922434c. Epub 2009 Dec 7.

Abstract

Thiopeptides, or thiazolylpeptides, are a family of highly modified peptide antibiotics first discovered several decades ago. Dozens of thiopeptides have since been identified, but, until recently, the biosynthetic genes responsible for their production remained elusive. The biosynthetic systems for a handful of thiopeptide metabolites were identified in the first portion of 2009. The surprising finding that these metabolites arise from the enzymatic tailoring of a simple, linear, ribosomally-synthesized precursor peptide led to a renewed appreciation of the architectural complexity accessible by posttranslational modification. This recent progress toward understanding thiopeptide antibiotic biosynthesis benefits the discovery of novel thiopeptides by either directed screening techniques or by mining available microbial genome sequences. Furthermore, access to the biosynthetic machinery now opens an avenue to the biosynthetic engineering of thiopeptide analogs. This Highlight discusses the genetic and biochemical insights revealed by these initial reports of the biosynthetic gene clusters for thiopeptide metabolites.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / biosynthesis*
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Molecular Sequence Data
  • Molecular Structure
  • Peptide Biosynthesis
  • Peptides / genetics
  • Peptides / metabolism*
  • Sequence Homology, Nucleic Acid
  • Sulfhydryl Compounds / metabolism*

Substances

  • Anti-Bacterial Agents
  • Peptides
  • Sulfhydryl Compounds