Genome Mining and Enzymatic Total Biosynthesis of Purincyclamide

Org Lett. 2019 Sep 6;21(17):6825-6829. doi: 10.1021/acs.orglett.9b02461. Epub 2019 Aug 13.

Abstract

A cyclodipeptide synthase-containing gene cluster (pcm) was identified in Streptomyces chrestomyceticus NA4264 through genome mining. Heterologous expression of the cryptic pcm gene cluster in Streptomyces albus led to the production of a new highly modified cyclodipeptide named purincyclamide (1). Bioinformatic analysis and gene knockout experiments revealed the biosynthetic pathway. The production of 1 was achieved through a one-pot enzymatic reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Molecular Structure
  • Peptide Synthases / chemistry
  • Peptide Synthases / genetics
  • Peptide Synthases / metabolism*
  • Purines / biosynthesis*
  • Purines / chemistry
  • Purines / isolation & purification
  • Streptomyces / enzymology*
  • Sulfonylurea Compounds / chemistry
  • Sulfonylurea Compounds / isolation & purification
  • Sulfonylurea Compounds / metabolism*

Substances

  • Purines
  • Sulfonylurea Compounds
  • tolcyclamide
  • Peptide Synthases
  • purine

Supplementary concepts

  • Streptomyces chrestomyceticus