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

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

Author information

1
Department of Chemistry and Biochemistry, Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, 90095, USA.
2
Stanford Genome Technology Center, Stanford University, Palo, CA, 93404, USA.

Abstract

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

PMID:
28679030
PMCID:
PMC5580239
DOI:
10.1002/anie.201705237
[Indexed for MEDLINE]
Free PMC Article

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