Unknown

Dataset Information

0

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 significant contribution to the prevention of diabetes, dyslipidemia, and Alzheimer's disease. (120 words/200 words).

SUBMITTER: Shi X 

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

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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

Shi Xuan X   Miyakawa Takuya T   Nakamura Akira A   Hou Feng F   Hibi Makoto M   Ogawa Jun J   Kwon Yeondae Y   Tanokura Masaru M  

Scientific reports 20171020 1

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) t  ...[more]

Similar Datasets

Unknown 2-Ketoglutarate-Generated In Vitro Enzymatic Biosystem Facilitates Fe(II)/2-Ketoglutarate-Dependent Dioxygenase-Mediated C-H Bond Oxidation for (2s,3r,4s)-4-Hydroxyisoleucine Synthesis.
| S-EPMC7432852 | biostudies-literature
Unknown Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines.
| S-EPMC4362023 | biostudies-literature
Unknown (3R,4S,5S)-4-Hydr-oxy-3-methyl-5-[(2S,3R)-3-methyl-pent-4-en-2-yl]tetra-hydro-furan-2-one.
| S-EPMC2962143 | biostudies-literature
Unknown (2S,3R,4S,4aR)-2,3,4,7-Tetra-hydroxy-3,4,4a,5-tetra-hydro-[1,3]dioxolo[4,5-j]phenanthridin-6(2H)-one hemihydrate.
| S-EPMC3588326 | biostudies-literature
Unknown (3S,4S,5S)-4-Hydr-oxy-3-methyl-5-[(2S,3R)-3-methyl-pent-4-en-2-yl]-4,5-dihydro-furan-2(3H)-one.
| S-EPMC2960667 | biostudies-literature
Unknown (3S,4S,5R)-4-Hydr-oxy-3-methyl-5-[(2S,3R)-3-methyl-pent-4-en-2-yl]-4,5-dihydro-furan-2(3H)-one.
| S-EPMC2968068 | biostudies-literature
Unknown 5-{(2S,3R,4S,5S,6R)-3,4-Dihydr-oxy-6-hydroxy-meth-yl-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydr-oxy-6-methyl-tetra-hydro-pyran-2-yloxy]tetra-hydro-pyran-2-yloxy}--7-hydr-oxy-2-(4-hydroxy-phen-yl)chromen-4-one monohydrate.
| S-EPMC2959284 | biostudies-literature
Unknown Engineering of Thermostable ?-Hydroxyacid Dehydrogenase for the Asymmetric Reduction of Imines.
| S-EPMC7756219 | biostudies-literature
Unknown (3R,4S)-3,4-Isopropyl-idenedioxy-3,4-dihydro-2H-pyrrole 1-oxide.
| S-EPMC3089370 | biostudies-literature
Unknown Structure-guided design of Serratia marcescens short-chain dehydrogenase/reductase for stereoselective synthesis of (R)-phenylephrine.
| S-EPMC5797133 | biostudies-literature