Structure-based mutagenesis of the malonyl-CoA:acyl carrier protein transacylase from Streptomyces coelicolor

Andrew T. Koppisch, Chaitan Khosla

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20 Scopus citations


Malonyl-CoA:acyl carrier protein transacylase (MAT) provides acyl-ACP thioesters for the biosynthesis of aromatic polyketides, and thus is the primary gatekeeper of substrate specificity in type II PKS. A recent report described the X-ray crystal structure of the Streptomyces coelicolor MAT and suggested active site residues which may be important for substrate selectivity [Keatinge-Clay, A. T., et al. (2003) Structure 11, 147-154]. Mutants were made to test the proposed roles of these residues, and the enzymes were characterized kinetically with respect to native and non-native substrates. The activity of the MAT was observed to be greatly attenuated in many of the observed mutants; however, the Km for malonyl-CoA was only modestly affected. Our results suggest the MAT uses an active site that is rigorously ordered around the acyl-thioester moiety of the acyl-CoA to facilitate rapid and efficient transacylation to an ACP. Our results also suggest that the MAT does not discriminate against α-substituted acyl-CoA thioesters solely on the basis of substrate size.

Original languageEnglish (US)
Pages (from-to)11057-11064
Number of pages8
Issue number37
StatePublished - Sep 23 2003

ASJC Scopus subject areas

  • Biochemistry


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