Bjarnesen Daniela, Lanza Lucrezia, Presini Francesco, Giovannini Pier Paolo, Müller Michael
Institute of Pharmaceutical Sciences, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via L. Borsari 46, 44121, Ferrara, Italy.
Chembiochem. 2025 Jul 11;26(13):e202500200. doi: 10.1002/cbic.202500200. Epub 2025 May 27.
Thiamine diphosphate (ThDP)-dependent enzymes are well known biocatalysts for CC 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 ThDP-dependent enzymes (e.g., decarboxylase, DC; transketolase, TK; α-keto acid dehydrogenase 2, αKADH2) that form tertiary alcohols, focusing on the substrate scope and diversity of physiological functions. The available toolbox and the characterized reactions shall serve as a starting point for future studies. Inspired by nature, an even broader diversity of classes and substrate specificities is expected in this field.
硫胺素二磷酸（ThDP）依赖性酶是众所周知的用于碳-碳键形成反应的生物催化剂。虽然这类酶主要用于研究仲醇偶姻的形成，但最近的研究已将其应用范围扩展到在不对称碳连接反应中利用酮作为亲电试剂来形成叔醇。手性叔醇是天然产物中普遍存在的结构单元，也是合成生物活性化合物的重要基石。由于可能的底物组合多样、起始原料易得、对映选择性高以及催化性ThDP辅因子具有有利的自我再生能力，ThDP依赖性酶正成为合成多种产物最有前景的生物催化剂类别之一。本综述概述了形成叔醇的ThDP依赖性酶（例如，脱羧酶、DC；转酮醇酶、TK；α-酮酸脱氢酶2、αKADH2），重点关注底物范围和生理功能的多样性。可用的工具箱和已表征的反应应作为未来研究的起点。受自然启发，预计该领域会出现更多种类和底物特异性的酶。
