An iterative type I polyketide synthase PKSN catalyzes synthesis of the decaketide alternapyrone with regio-specific octa-methylation

Chem Biol. 2005 Dec;12(12):1301-9. doi: 10.1016/j.chembiol.2005.09.015.

Abstract

A biosynthetic gene cluster containing five genes, alt1-5, was cloned from Alternaria solani, a causal fungus of early blight disease to tomato and potato. Homology searching indicated that the alt1, 2, and 3 genes code for cytochrome P450s and the alt4 gene for a FAD-dependent oxygenase/oxidase. The alt5 gene encodes a polyketide synthase (PKS), named PKSN, that was found to be an iterative type I complex reduced-type PKS with a C-methyltransferase domain. To identify the PKSN function, the alt5 gene was introduced into the fungal host Aspergillus oryzae under an alpha-amylase promoter. The transformant produced a polyketide compound, named alternapyrone, whose structure is shown to be 3,5-dimethyl-4-hydroxy-6-(1,3,5,7,11,13-hexamethyl-3,5,11-pentadecatrienyl)-pyran-2-one. Labeling experiments confirmed that alternapyrone is a decaketide with octa-methylation from methionine on every C(2) unit except the third unit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternaria / enzymology
  • Alternaria / genetics*
  • Amino Acid Sequence
  • Aspergillus oryzae / genetics*
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism
  • Molecular Sequence Data
  • Molecular Structure
  • Polyketide Synthases / genetics*
  • Polyketide Synthases / metabolism
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Triterpenes / chemistry
  • Triterpenes / metabolism*

Substances

  • 3,5-dimethyl-4-hydroxy-6-(1,3,5,7,11,13-hexamethyl-3,5,11-pentadecatrienyl)pyran-2-one
  • Triterpenes
  • Polyketide Synthases
  • Methyltransferases

Associated data

  • GENBANK/AB120221