Identification and characterization of the cuevaene A biosynthetic gene cluster in streptomyces sp. LZ35

Chembiochem. 2013 Aug 19;14(12):1468-75. doi: 10.1002/cbic.201300316. Epub 2013 Jul 3.

Abstract

Genome sequence analysis of Streptomyces sp. LZ35 has revealed a large number of secondary metabolite pathways, including one encoded in an orphan type I polyketide synthase gene cluster that contains a putative chorismatase/3-hydroxybenzoate synthase gene. Mutagenesis and comparative metabolic profiling led to the identification of cuevaene A as the metabolic product of the gene cluster, thus making it the first 3-HBA containing polyketide biosynthetic gene cluster described to date. Cuv10 was proven to be responsible for the conversion of chorismate into 3-HBA; Cuv18 is speculated to be responsible for the 6-hydroxylation of 3-HBA during polyketide chain elongation. Additionally, several pathway-specific regulatory factors that affect the production of cuevaene A were identified. Our results indicate that targeted inactivation of a gene followed by comparative metabolic profiling is a useful approach to identify and characterize cryptic biosynthetic gene clusters.

Keywords: 3-hydroxybenzoate synthase; antibiotics; biosynthesis; cuevaene A; orphan gene cluster.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzofurans / chemistry
  • Chromatography, High Pressure Liquid
  • Fatty Acids, Unsaturated / chemistry
  • Fatty Acids, Unsaturated / genetics
  • Molecular Structure
  • Multigene Family*
  • Streptomyces / classification
  • Streptomyces / genetics*

Substances

  • Benzofurans
  • Fatty Acids, Unsaturated
  • cuevaene A