Laboratory of Basic Science on Healthy Longevity, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Industrial Microbiology, Graduate School of Agriculture, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan.
Sci Rep. 2017 Oct 20;7(1):13703. doi: 10.1038/s41598-017-13978-w.
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 significant contribution to the prevention of diabetes, dyslipidemia, and Alzheimer's disease. (120 words/200 words).
葫芦巴是一种抗衰老和促进人体健康的膳食补充剂。（2S，3R，4S）-4-羟基异亮氨酸（4-HIL）是从葫芦巴种子中提取的，由于其胰岛素样作用，有望成为治疗糖尿病和糖尿病肾病的有前途的口服药物。尽管已经提出了几种 4-HIL 的化学合成方法，但这些方法需要多步反应来控制 4-HIL 的立体化学。在这项研究中，我们修饰了关键酶 4-HIL 脱氢酶（HILDH），以克服 4-HIL 商业规模生产的最大限制。结果，成功地实现了有效的羰基还原，以严格的立体选择性（>99% de）生产（2S，3R，4S）-4-HIL。通过我们的合成方法大规模生产（2S，3R，4S）-4-HIL 可能对预防糖尿病、血脂异常和阿尔茨海默病有重大贡献。（120 个单词/200 个单词）。
