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PDBsum entry 5gwt
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Oxidoreductase
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PDB id
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5gwt
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References listed in PDB file
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Key reference
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Title
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Engineering a short-Chain dehydrogenase/reductase for the stereoselective production of (2s,3r,4s)-4-Hydroxyisoleucine with three asymmetric centers.
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Authors
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X.Shi,
T.Miyakawa,
A.Nakamura,
F.Hou,
M.Hibi,
J.Ogawa,
Y.Kwon,
M.Tanokura.
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Ref.
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Sci Rep, 2017,
7,
13703.
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PubMed id
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Abstract
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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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