Biosynthesis of the anti-infective marformycins featuring pre-NRPS assembly line N-formylation and O-methylation and post-assembly line C-hydroxylation chemistries

Org Lett. 2015 Mar 20;17(6):1509-12. doi: 10.1021/acs.orglett.5b00389. Epub 2015 Mar 6.

Abstract

The biosynthetic gene cluster governing production of anti-infective marformycins was identified from deep sea-derived Streptomyces drozdowiczii SCSIO 10141. The putative mfn gene cluster (45 kb, 20 orfs) was found to encode six NRPSs and related proteins for cyclodepsipeptide core construction (mfnCDEFKL), a methionyl-tRNA formyltransferase (mfnA), a SAM-dependent methyltransferase (mfnG), and a cytochrome P450 monooxygenase for piperazic acid moiety hydroxylation (mfnN); notably, only MfnN uses an intact cyclodepsipeptide intermediate as its substrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / metabolism*
  • Cytochrome P-450 Enzyme System / metabolism
  • Depsipeptides / chemistry*
  • Hydroxylation
  • Hydroxymethyl and Formyl Transferases / metabolism
  • Marine Biology
  • Methylation
  • Molecular Structure
  • Multigene Family
  • Peptide Synthases / metabolism*
  • Streptomyces / chemistry*
  • Streptomyces / genetics

Substances

  • Anti-Infective Agents
  • Depsipeptides
  • Cytochrome P-450 Enzyme System
  • Hydroxymethyl and Formyl Transferases
  • methionyl-tRNA formyltransferase
  • Peptide Synthases
  • non-ribosomal peptide synthase