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Stereoselectivity and Expanded Substrate Scope of an Engineered PLP-Dependent Aldolase

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  • We thank the ETH Zürich, the University of Zürich, and the Schweizerischer Nationalfonds for financial support. PLP=pyridoxal 5′-phosphate.

Abstract

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Optimizing the active site: A pyridoxal 5′-phosphate(PLP)-dependent alanine racemase was converted into a retro-aldolase by a single active-site mutation. This new catalyst reacts efficiently with quaternary β-hydroxy α-amino acids, a class of molecules that natural aldolases have not been evolved to handle. Computational docking experiments suggest a novel mechanism for this process and rationalize the stereochemical preferences of the enzyme.

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