- Practical application of recombinant whole-cell biocatalysts for the manufacturing of pharmaceutical intermediates such as chiral alcohols
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We have developed efficient biocatalytic processes for the preparation of chiral alcohols, such as (R)-1,3-butanediol, ethyl (S)-4-chloro-3-hyroxybutanoate, ethyl (R)-4-chloro-3-hyroxybutanoate, (S)-5-chloro-2-pentanol, (R)-5-chloro-2-pentanol, and (S)-cyclopropylethanol by stereospecific enzymatic oxidoreduction on a practical level. These chiral alcohols are very important synthons for the synthesis of various pharmaceutical intermediates that lead to antibiotics and inhibitors of HMG-CoA reductase. Here, we present practical applications on biocatalysis using novel recombinant whole-cell biocatalysts that catalyzed enantioselective oxidation and asymmetric reduction with a coenzyme regeneration system.
- Matsuyama, Akinobu,Yamamoto, Hiroaki,Kobayashi, Yoshinori
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p. 558 - 561
(2013/09/06)
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- A Pseudomonas sp. Alcohol Dehydrogenase with Broad Substrate Specificity and Unusual Stereospecificity for Organic Synthesis
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A new alcohol dehydrogenase from Pseudomonas sp. strian PED has been isolated and characterized.The enzyme exhibits a broad substrate specificity, accepting aromatic, cyclic, and aliphatic compounds as substrates.The Km values were determined as 525 μM for NAD and 75 μM for 2-propanol with a specific activity of 36 U/mg.The kinetic mechanism is ordered bi-bi with the cofactor binding first and releasing last.The enzyme transfers the pro-R hydride of NADH to the si face of carbonyl compounds to yield (R) alcohols.Synthetic-scale reductions of a number of representative compounds were carried out in high enentiomeric excess with in situ regeneration of NADH using 2-propanol as the hydride source and the same enzyme as catalyst.
- Bradshaw, Curt W.,Fu, Hong,Shen, Gwo-Jenn,Wong, Chi-Huey
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p. 1526 - 1532
(2007/10/02)
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- Lactobacillus kefir Alcohol Dehydrogenase: A Useful Catalyst for Synthesis
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The alcohol dehydrogenase from Lactobacillus kefir simultaneously catalyzes carbonyl reductions and NADPH regeneration in the presence of 2-propanol.Representative synthesis of a number of chiral alcohols was accomplished in good yield and high enantiomeric excess (94-99percent).This NADPH-requiring enzyme transfers the pro-R hydride from the cofactor to the si face of carbonyls to give (R) alcohols.The enzyme exhibits a very broad substrate specificity and high enantioselectivity for the synthesis of chiral aromatic, cyclic, polycyclic, and aliphatic alcohols.
- Bradshaw, Curt W.,Hummel, Werner,Wong, Chi-Huey
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p. 1532 - 1536
(2007/10/02)
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- A New NAD-dependent Alcohol Dehydrogenase with Opposite Facial Selectivity useful for Asymmetric Reduction and Cofactor Regeneration
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A new NAD-dependent alcohol dehydrogenase isolated from a Pseudomonas species catalysed the reduction of many acyclic ketones to optically active alcohols with very high enantioselectivity (90 to >98percent enantiomeric excess); the stereochemical course of the reduction was determined to be the transfer of the pro-(R) hydrogen from NADH to the Si face of the carbonyl group, a process different from that for other known alcohol dehydrogenases.
- Shen, Gwo-Jenn,Wang, Yi-Fong,Bradshaw, Curt,Wong, Chi-Huey
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p. 677 - 679
(2007/10/02)
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