Characterization of the Ketosynthase and Acyl Carrier Protein Domains at the LnmI Nonribosomal Peptide Synthetase-Polyketide Synthase Interface for Leinamycin Biosynthesis

Org Lett. 2016 Sep 2;18(17):4288-91. doi: 10.1021/acs.orglett.6b02033. Epub 2016 Aug 19.

Abstract

Leinamycin (LNM) is biosynthesized by a hybrid nonribosomal peptide synthetase (NRPS)-acyltransferase (AT)-less type I polyketide synthase (PKS). Characterization of LnmI revealed ketosynthase (KS)-acyl carrier protein (ACP)-KS domains at the NRPS-PKS interface. Inactivation of the KS domain or ACP domain in vivo abolished LNM production, and the ACP domain can be phosphopantetheinylated in vitro. The LnmI KS-ACP-KS architecture represents a new mechanism for functional crosstalk between NRPS and AT-less type I PKS in the biosynthesis of hybrid peptide-polyketide natural products.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acyl Carrier Protein / chemistry
  • Acyl Carrier Protein / metabolism*
  • Lactams / chemistry
  • Lactams / metabolism*
  • Macrolides / chemistry
  • Macrolides / metabolism*
  • Molecular Conformation
  • Peptide Synthases / chemistry
  • Peptide Synthases / metabolism*
  • Polyketide Synthases / chemistry
  • Polyketide Synthases / metabolism*
  • Protein Domains
  • Thiazoles / chemistry
  • Thiazoles / metabolism*
  • Thiones / chemistry
  • Thiones / metabolism*

Substances

  • Acyl Carrier Protein
  • Lactams
  • Macrolides
  • Thiazoles
  • Thiones
  • leinamycin
  • Polyketide Synthases
  • Peptide Synthases
  • non-ribosomal peptide synthase