Structural basis of keto acid utilization in nonribosomal depsipeptide synthesis

Nat Chem Biol. 2020 May;16(5):493-496. doi: 10.1038/s41589-020-0481-5. Epub 2020 Feb 17.

Abstract

Nonribosomal depsipeptides are natural products composed of amino and hydroxy acid residues. The hydroxy acid residues often derive from α-keto acids, reduced by ketoreductase domains in the depsipeptide synthetases. Biochemistry and structures reveal the mechanism of discrimination for α-keto acids and a remarkable architecture: flanking intact adenylation and ketoreductase domains are sequences separated by >1,100 residues that form a split 'pseudoAsub' domain, structurally important for the depsipeptide module's synthetic cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / chemistry
  • Bacillus / enzymology
  • Bacterial Proteins / chemistry
  • Crystallography, X-Ray
  • Depsipeptides / biosynthesis*
  • Depsipeptides / chemistry
  • Keto Acids / chemistry*
  • Keto Acids / metabolism
  • Lysine / metabolism
  • Peptide Synthases / chemistry*
  • Peptide Synthases / genetics
  • Peptide Synthases / metabolism*
  • Protein Conformation
  • Protein Domains

Substances

  • Bacterial Proteins
  • Depsipeptides
  • Keto Acids
  • Alcohol Oxidoreductases
  • polyketide synthase ketoreductase
  • Peptide Synthases
  • Lysine

Supplementary concepts

  • Bacillus stratosphericus