Biosynthesis of LL-Z1272β: Discovery of a New Member of NRPS-like Enzymes for Aryl-Aldehyde Formation

Chembiochem. 2016 May 17;17(10):904-7. doi: 10.1002/cbic.201600087. Epub 2016 Apr 9.

Abstract

LL-Z1272β (1) is a prenylated aryl-aldehyde produced by several fungi; it also serves as a key pathway intermediate for many fungal meroterpenoids. Despite its importance in the biosynthesis of natural products, the molecular basis for the biosynthesis of 1 has yet to be elucidated. Here we identified the biosynthetic gene cluster for 1 from Stachybotrys bisbyi PYH05-7, and elucidated the biosynthetic route to 1. The biosynthesis involves a polyketide synthase, a prenyltransferase, and a nonribosomal peptide synthetase (NRPS)-like enzyme, which is responsible for the generation of the aldehyde functionality. Interestingly, the NRPS-like enzyme only accepts the farnesylated substrate to catalyze the carboxylate reduction; this represents a new example of a substrate for adenylation domains.

Keywords: aryl-aldehyde; biosynthesis; carboxylate reductase; enzymes; meroterpenoids.

MeSH terms

  • Aldehydes / chemistry
  • Aspergillus / enzymology
  • Aspergillus / genetics
  • Benzaldehydes / chemistry
  • Benzaldehydes / metabolism*
  • Chromatography, High Pressure Liquid
  • Multigene Family
  • Peptide Synthases / genetics
  • Peptide Synthases / metabolism*
  • Polyketide Synthases / genetics
  • Polyketide Synthases / metabolism*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / metabolism*
  • Stachybotrys / chemistry
  • Stachybotrys / metabolism

Substances

  • Aldehydes
  • Benzaldehydes
  • LL-Z1272beta
  • Sesquiterpenes
  • Polyketide Synthases
  • Peptide Synthases
  • non-ribosomal peptide synthase