Methanol-based industrial biotechnology: current status and future perspectives of methylotrophic bacteria.

Methanol is one of the building blocks in the chemical industry and can be synthesized either from petrochemical or renewable resources, such as biogas. Bioprocess technology with methylotrophic bacteria is well established, as illustrated by large-scale single-cell protein production in the past. During recent years, the first genomes of methylotrophs have been sequenced and significant progress in elucidating their metabolism has been made. In addition, the tool set for genetic engineering of methylotrophic bacteria has expanded greatly and strategies to produce fine and bulk chemicals with methylotrophs have been described. This review highlights the potential of these bacteria for the development of economically competitive bioprocesses based on methanol as an alternative carbon source, bringing together biological, technical and economic considerations.

Chemoenzymatic synthesis of the chiral side-chain of statins: application of an alcohol dehydrogenase catalysed ketone reduction on a large scale.

The chemoenzymatic synthesis of the tert-butyl (S)-6-chloro-5-hydroxy-3-ketohexanoate is described. Our approach relies on a highly regio- and enantioselective reduction of a beta,delta-diketohexanoate ester catalysed by NADP(H)-dependent alcohol dehydrogenase of Lactobacillus brevis (LBADH). A detailed description of the scale-up of the enzymatic synthesis of the hydroxyketo ester is given which includes a scale-up of the substrate synthesis as well, i.e. the preparation of diketo ester on a 100 g scale. Furthermore, studies directed towards improving the co-catalyst [NADP(H)] consumption of the enzymatic key step by kinetic studies and application of a biphasic reaction medium were performed.