Johanson Ted, Katz Michael, Gorwa-Grauslund Marie F
Department of Applied Microbiology, Lund University, P.O. Box 124, SE-22100 Lund, Sweden.
FEMS Yeast Res. 2005 Apr;5(6-7):513-25. doi: 10.1016/j.femsyr.2004.12.006.
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 baker's yeast Saccharomyces cerevisiae can notably reduce dicarbonyl compounds (in particular alpha- and beta-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.
在制药和化学工业中，纯手性分子作为生产药物或精细化学品的中间体是必需的。微生物是化学合成的一种有吸引力的替代方法，因为它们有潜力以高对映体过量（ee）生成单一立体异构体。面包酵母酿酒酵母能显著地将二羰基化合物（特别是α-和β-二酮及酮酯）还原为具有高ee的手性醇。然而，产物形成速率较低。此外，几乎所有已知的二羰基还原反应中，NADPH作为首选的辅酶因子，其再生需要大量的共底物。传统上，通过工艺工程可实现更好的ee、还原速率和产物滴度。重组DNA技术的出现为通过菌株工程提高生产率和产量提供了另一种策略。本综述讨论了菌株工程的两个方面：（i）生成对二羰基化合物具有更高还原酶活性的菌株，以及（ii）优化用于NADPH辅酶因子再生的共底物利用。
