Strain engineering for stereoselective bioreduction of dicarbonyl compounds by yeast reductases

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• 作者：Johanson ; Ted ; Katz ; Michael ; Gorwa-Grauslund ; Marie F.
• 关键词：Whole-cell bioreductions ; Strain engineering ; Reductase ; Yeast ; Dicarbonyl ; NADPH availability
• 刊名：FEMS Yeast Research
• 出版年：2005
• 出版时间：April, 2005
• 年：2005
• 卷：5
• 期：6-7
• 页码：513-525
• 全文大小：270 K

文摘

Pure chiral molecules are needed in the pharmaceutical and chemical industry as intermediates for the production of drugs or fine chemicals. Microorganisms represent an attractive alternative to chemical synthesis since they have the potential to generate single stereoisomers in high enantiomeric excess (ee). The bakeraaas yeast Saccharomyces cerevisiae can notably reduce dicarbonyl compounds (in particular aa- and aa-diketones and keto esters) to chiral alcohols with high ee. However, products are formed at a low rate. Moreover, large amounts of co-substrate are required for the regeneration of NADPH that is the preferred co-factor in almost all the known dicarbonyl reductions. Traditionally, better ee, reduction rate and product titre have been achieved via process engineering. The advent of recombinant DNA technology provides an alternative strategy to improve productivity and yield by strain engineering. This review discusses two aspects of strain engineering: (i) the generation of strains with higher reductase activity towards dicarbonyl compounds and (ii) the optimisation of co-substrate utilisation for NADPH cofactor regeneration.