Amidjojo Maya, Franco-Lara Ezequiel, Nowak Alessandro, Link Hannes, Weuster-Botz Dirk
Institute of Biochemical Engineering, Munich University of Technology, Boltzmannstrasse 15, 85748 Garching, Germany.
Appl Microbiol Biotechnol. 2005 Nov;69(1):9-15. doi: 10.1007/s00253-005-1921-6. Epub 2005 Oct 20.
An efficient whole cell biotransformation process using Lactobacillus kefir was developed for the asymmetric synthesis of tert-butyl (3R, 5S) 6-chloro-dihydroxyhexanoate, a chiral building block for the HMG-CoA reductase inhibitor. The effects of buffer concentration, temperature, pH and oxygen on the asymmetric reduction were investigated in batch reactions. Improvements in final product concentration and yields of 153% (120 mM) and 79% (0.85 mol/mol) with respect to the batch-process were achieved in an optimised fed-batch process. The pure substrate tert-butyl-6-chloro-3,5-dioxohexanoate was dispersed as microdroplets into the reaction system. This resulted in a space-time yield of 4.7 mmol l(-1) h(-1). A diastereomeric excess of >99% was measured for (3R, 5S) and (3S, 5S) tert-butyl 6-chloro-dihydroxyhexanoate.
开发了一种使用开菲尔乳杆菌的高效全细胞生物转化过程，用于不对称合成叔丁基（3R，5S）6-氯-二羟基己酸酯，这是一种用于HMG-CoA还原酶抑制剂的手性构建模块。在分批反应中研究了缓冲液浓度、温度、pH值和氧气对不对称还原的影响。在优化的补料分批过程中，相对于分批过程，最终产物浓度提高了153%（120 mM），产率提高了79%（0.85 mol/mol）。纯底物叔丁基-6-氯-3,5-二氧代己酸酯以微滴形式分散到反应体系中。这导致时空产率为4.7 mmol l(-1) h(-1)。测得（3R，5S）和（3S，5S）叔丁基6-氯-二羟基己酸酯的非对映体过量>99%。
