A heptaketide naphthaldehyde produced by a polyketide synthase from Nectria haematococca

Bioorg Med Chem Lett. 2012 Jul 1;22(13):4338-40. doi: 10.1016/j.bmcl.2012.05.005. Epub 2012 May 9.

Abstract

Bostrycoidin and fusarubin are biologically active fungal polyketides produced by Nectria haematococca. This azaanthraquinone and naphthoquinone are thought to be biosynthesized via formation of a C(14) heptaketide aldehyde as a common key intermediate. A BLAST search against the genome of N. haematococca revealed one candidate gene (NECHADRAFT_101778, NhPKS1), which encodes a multi-domain polyketide synthase (PKS) with a thiol reductase (TR) domain that would facilitate the reductive release of the intermediate to produce a free aldehyde. To investigate the possible involvement of NhPKS1 in the biosynthesis of bostrycoidin and fusarubin, NhPKS1 was heterologously expressed in Aspergillus oryzae, and shown to produce a heptaketide 3-acetonyl-1,6,8-trihydroxy-2-naphthaldehyde as a single product. Thus, NhPKS1 catalyzes a C-2/C-11 and C-4/C-9 aldol-type cyclization of a linear intermediate followed by a subsequent reductive product release to yield the naphthaldehyde. The results indicate NhPKS1 is the enzyme involved in the biosynthesis of bostrycoidin and fusarubin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism*
  • Aspergillus oryzae / metabolism
  • Cyclization
  • Isoquinolines / chemistry
  • Isoquinolines / metabolism
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Multienzyme Complexes / metabolism
  • Naphthalenes / metabolism*
  • Naphthoquinones / metabolism
  • Nectria / enzymology*
  • Polyketide Synthases / genetics
  • Polyketide Synthases / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Aldehydes
  • Isoquinolines
  • Multienzyme Complexes
  • Naphthalenes
  • Naphthoquinones
  • Recombinant Proteins
  • bostrycoidin
  • 2-naphthaldehyde
  • Polyketide Synthases