Engineering an efficient and enantioselective enzyme for the Morita-Baylis-Hillman reaction.

ABSTRACT: The combination of computational design and directed evolution could offer a general strategy to create enzymes with new functions. So far, this approach has delivered enzymes for a handful of model reactions. Here we show that new catalytic mechanisms can be engineered into proteins to accelerate more challenging chemical transformations. Evolutionary optimization of a primitive design afforded an efficient and enantioselective enzyme (BH32.14) for the Morita-Baylis-Hillman (MBH) reaction. BH32.14 is suitable for preparative-scale transformations, accepts a broad range of aldehyde and enone coupling partners and is able to promote selective monofunctionalizations of dialdehydes. Crystallographic, biochemical and computational studies reveal that BH32.14 operates via a sophisticated cataly

SUBMITTER: Crawshaw R 

PROVIDER: S-EPMC7612480 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature