Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-13978-w
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Funding
- Targeted Proteins Research Program (TPRP) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT)
- Japan Society for the Promotion of Science (JSPS) [23228003, 24688010]
- Grants-in-Aid for Scientific Research [17H05835, 24688010] Funding Source: KAKEN
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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)
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