Engineering a short-chain dehydrogenase/reductase for the stereoselective production of (2S,3R,4S)-4-hydroxyisoleucine with three asymmetric centers.

ABSTRACT: Fenugreek is a dietary supplement for anti-aging and human health. (2S,3R,4S)-4-hydroxyisoleucine (4-HIL), which is extracted from fenugreek seeds, is expected to be a promising orally active drug for diabetes and diabetic nephropathy because of its insulinotropic effect. Although several chemical synthesis methods of 4-HIL have been proposed, these methods require multistep reactions to control the stereochemistry of 4-HIL. In this study, we modified the key enzyme 4-HIL dehydrogenase (HILDH) to overcome the biggest limitation in commercial-scale production of 4-HIL. As a result, an effective one-step carbonyl reduction to produce (2S,3R,4S)-4-HIL was successfully accomplished with strict stereoselectivity (>99% de). Mass production of (2S,3R,4S)-4-HIL by our synthetic method could have a

SUBMITTER: Shi X 

PROVIDER: S-EPMC5651801 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature