酵母による光学活性アルコール類製造のためのリアクターに関する研究
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概要
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Large-scale production of chiral alcohols with bakers' yeast was effectively performed by examining the regeneration system of nicotineamide coenzymes in cells. First, a new procedure for the asymmetric reduction of prochiral ketones was developed, based on the use of ethanol instead of carbohydrate as the energy source for NAD(P)H regeneration. In the asymmetric reduction of ethyl acetoacetate (EA), both the yield and the optical purity of the product, (S)-ethyl 3-hydroxybutanoate (E 3-HB), were considerably improved by applying fed-batch operation to the new procedure. (S)-E 3-HB with >99% enantiomeric excess was effectively prepared on a large scale using a bubblecolumn reactor. Also, acetol was reduced to (R)-propylene glycol (PG), a useful chiral building block, in the same manner. A total scheme for NAD(P)H regeneration from NAD(P)^+ through the oxidative pathway of ethanol was proposed. The relationship between the condition of the oxygen supply and the efficiency (ν_<substrate>/ν_<EtOH>) was evaluated. Next, an enantioselective oxidation for preparing other chiral alcohols such as (S)-PG was developed. Treatment of a racemic 1,2-alkanediol with bakers' yeast followed by removal of the oxidation product, 1-hydroxy-2-alkanone, affords (S)-1,2-alkanediol. The outline of the oxidation, especially the relationship to oxygen transfer for regenerating NAD^+ from NADH, was estimated. Finally, the microbial resolution of racemic 1,2-alkanediols was performed on a large scale by repeating the procedures with bakers' yeast, the oxidative resolution of racemic 1,2-alkanediols followed by the asymmetric reduction of the oxidation products.
- 社団法人日本生物工学会の論文
- 1995-07-25
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