Synthesis of cyclic chiral alpha-hydroxy ketones by a novel medium-chain zinc-dependent alcohol dehydrogenase from Thauera aromatica (ThaADH)

Zinc-dependent alcohol dehydrogenases (ADHs) are valuable biocatalysts for enantiopure synthesis of chiral compounds, such as alpha-hydroxy ketones, which are important building blocks for applications in pharmaceutical industry and fine chemistry sector. A wide range of ADHs accepts aliphatic and aromatic diketones as substrates for reduction to alpha-hydroxy ketones or diols. Among these ADHs, in our workgroup research is focused on carbonyl reductase from Candida parapsilosis (CPCR2). However, most of these well characterized ADHs are not able to reduce cyclic diketones.

A promising exception is a novel zinc-dependent alcohol dehydrogenase from Thauera aromatica (ThaADH), which shows significant activity for reduction of cyclic alpha-diketones. The aim of this project is an overall characterization of this enzyme, with focus on the determination of structural determinants influencing the substrate specificity and stereoselectivity of ThaADH. Results should help to understand structure-function relationship of various medium-chain zinc-dependent alcohol dehydrogenases.