Reversible Product Release and Recapture by a Fungal Polyketide Synthase Using a Carnitine Acyltransferase Domain

Angew Chem Int Ed Engl. 2017 Aug 1;56(32):9556-9560. doi: 10.1002/anie.201705237. Epub 2017 Jul 5.


Fungal polyketides have significant biological activities, yet the biosynthesis by highly reducing polyketide synthases (HRPKSs) remains enigmatic. An uncharacterized group of HRPKSs was found to contain a C-terminal domain with significant homology to carnitine O-acyltransferase (cAT). Characterization of one such HRPKS (Tv6-931) from Trichoderma virens showed that the cAT domain is capable of esterifying the polyketide product with polyalcohol nucleophiles. This process is readily reversible, as confirmed through the holo ACP-dependent transesterification of the released product. The methyltransferase (MT) domain of Tv6-931 can perform two consecutive α-methylation steps on the last β-keto intermediate to yield an α,α-gem-dimethyl product, a new programing feature among HRPKSs. Recapturing of the released product by cAT domain is suggested to facilitate complete gem-dimethylation by the MT.

Keywords: acyltransferase; biosynthesis; heterologous expression; methyltransferase; polyketides.

Publication types

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

MeSH terms

  • Biocatalysis
  • Biological Products / chemistry
  • Biological Products / metabolism
  • Carnitine Acyltransferases / metabolism*
  • Catalytic Domain
  • Metabolomics
  • Molecular Structure
  • Polyketide Synthases / metabolism*
  • Trichoderma / enzymology*


  • Biological Products
  • Polyketide Synthases
  • Carnitine Acyltransferases