Engineering of the Thiamine Diphosphate-Dependent JanthE for the Synthesis of Tertiary Alcohols.

ABSTRACT: The development of (bio)catalytic methods to chiral tertiary alcohols is in demand, yet the enantioselective synthesis of tertiary alcohols with sterically hindered moieties is problematic. JanthE is a novel thiamine diphosphate-dependent enzyme that catalyzes aldehyde-ketone cross-coupling reactions with a wide range of donor and acceptor substrates. However, product formation is low and precludes large-scale production. We investigated the conversion of 2-oxobutanoate and the bulky ketone phenoxy-2-propanone to the product 2-hydroxy-2-methyl-1-phenoxypentan-3-one as a model reaction for the synthetic capabilities of JanthE. As the reaction design did not significantly improve the yield, we proceeded to rational protein engineering. Docking experiments identified V121, Y268, P293, Y297, a

SUBMITTER: Lanza L 

PROVIDER: S-EPMC12188165 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature