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

Autor:	Nicholas Liu, Leibniz Hang, Claire G. Page, Yi Tang, Maureen E. Hillenmeyer, Yiu-Sun Hung, Man-Cheng Tang, Jian Li, Colin J. B. Harvey
Rok vydání:	2017
Předmět:	0301 basic medicine Methyltransferase Stereochemistry 010402 general chemistry 01 natural sciences Catalysis Homology (biology) Article 03 medical and health sciences Polyketide chemistry.chemical_compound Biosynthesis Polyketide synthase Catalytic Domain medicine Metabolomics Carnitine Trichoderma Biological Products biology Molecular Structure Chemistry 010405 organic chemistry General Chemistry General Medicine 0104 chemical sciences 030104 developmental biology Biochemistry Carnitine Acyltransferases Acyltransferase biology.protein Biocatalysis Heterologous expression Polyketide Synthases medicine.drug
Zdroj:	Angewandte Chemie. 129:9684-9688
ISSN:	0044-8249
DOI:	10.1002/ange.201705237
Popis:	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.
Databáze:	OpenAIRE
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