Broad substrate specificity of ketoreductases derived from modular polyketide synthases.
Recombinant ketoreductase (KR) domains derived from antibiotic-producing modular polyketide synthases (PKSs) have been examined as potential catalysts for the enantioselective reduction of non-polyketide substrates. KR domains from two modular PKSs show significant activity toward alternative substrates, particularly those that incorporate cyclohexyl moieties. Through site-directed mutagenesis of the amino acid motifs previously implicated in stereocontrol by KRs, we have identified mutants with improved activity toward such compounds. These results suggest that PKS KRs could potentially be used as biotransformation catalysts for the production of chiral alcohols.
Bali
Shilpa
S
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
O'Hare
Helen M
HM
Weissman
Kira J
KJ
D020816:Amino Acid Motifs; D019020:Directed Molecular Evolution; D004591:Electrophoresis, Polyacrylamide Gel; D016297:Mutagenesis, Site-Directed; D010088:Oxidoreductases / Q000378:metabolism*; D048630:Polyketide Synthases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
D011994:Recombinant Proteins; D048630:Polyketide Synthases; D010088:Oxidoreductases