Aldehyde Dehydrogenase from Klebsiella pneumoniae: A Robust Biocatalyst for Preparing Heteroatom-Containing Carboxylic Acids

Heterocyclic scaffolds have broad applications in organic synthesis, resulting in the production of essential compounds utilized in pharmaceuticals, agrochemicals, and dietary products. In this study, we present the characterization of a discovered succinic semialdehyde dehydrogenase from Klebsiella pneumoniae (KpSSADH) and elucidate its crystallographic structure. Further investigation into the catalytic performance of KpSSADH reveals its remarkable efficiency in converting various heteroatom-containing (including N, S, O, and their combinations) cyclic aldehydes into the corresponding acids with conversions reaching up to 99%. To expand the range of available substrates, we designed cascade reactions by integrating thiol oxidase from Methylovorus sp. MP688 or unspecific peroxygenase from Agrocybe aegerita with KpSSADH. Through this approach, the desired acids via alcohol oxidation and C−H bond oxyfunctionalization were obtained, respectively. The discovery of KpSSADH and the envisioned cascade reactions have significantly broadened the biocatalytic toolbox for synthesizing heteroatom-containing carboxylic acids, thereby holding potential for applications in the modern pharmaceutical industry.