Diversity Of ThDP-Dependent Enzymes Forming Chiral Tertiary Alcohols.

Abstract

Thiamine diphosphate (ThDP)-dependent enzymes are well known biocatalysts for C-C bond-forming reactions. While this enzyme class is mainly investigated for the formation of acyloins of secondary alcohols, recent studies have expanded its scope to utilize ketones as electrophiles in asymmetric carboligation reactions for the formation of tertiary alcohols. Chiral tertiary alcohols are ubiquitous motifs in natural products and important building blocks for the synthesis of bioactive compounds. ThDP-dependent enzymes are emerging as one of the most promising classes of biocatalysts for synthesizing a wide range of products due to the variety of possible substrate combinations, accessible starting materials, high enantioselectivity, and advantageous self-regeneration of the catalytic ThDP cofactor. This review provides an overview of the tertiary alcohol-forming ThDP-dependent enzymes, focusing on the substrate scope, diversity of physiological functions, and future perspectives. Of nine superfamilies of ThDP-dependent enzymes, three (decarboxylases, DC; transketolases, TK; α-ketoacid dehydrogenase superfamily 2, αKADH2) are known to use ketones as acceptor substrates. It is unknown whether other superfamilies of ThDP-dependent enzymes hold similar potential. Inspired by nature, an even broader diversity of classes and substrate specificities is expected in this field.