Insights into the stereospecificity of ketoreduction in a modular polyketide synthase |
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Authors: | Kwan David H Tosin Manuela Schläger Nadin Schulz Frank Leadlay Peter F |
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Affiliation: | Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, UK CB2 1GA. |
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Abstract: | Ketoreductase enzymes are responsible for the generation of hydroxyl stereocentres during the biosynthesis of complex polyketide natural products. Previous studies of isolated polyketide ketoreductases have shown that the stereospecificity of ketoreduction can be switched by mutagenesis of selected active site amino acids. We show here that in the context of the intact polyketide synthase multienzyme the same changes do not alter the stereochemical outcome in the same way. These findings point towards additional factors that govern ketoreductase stereospecificity on intact multienzymes in vivo. |
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