Schmidt E, Ghisalba O, Gygax D, Sedelmeier G
Ciba-Geigy AG, Basle, Switzerland.
J Biotechnol. 1992 Jul;24(3):315-27. doi: 10.1016/0168-1656(92)90040-g.
(R)-2-Hydroxy-4-phenylbutyric acid, an intermediate in the manufacture of inhibitors of angiotensin converting enzyme, can be produced continuously in an enzyme membrane reactor by enzymatic reduction of its corresponding alpha-keto acid. D-Lactate dehydrogenase (D-LDH) from Staphylococcus epidermidis was chosen as the most appropriate enzyme to carry out the NADH-dependent reduction. Formate dehydrogenase (FDH) was used for NADH regeneration. Detailed kinetic measurements and a mathematical model for the coupled enzyme reactions were applied to calculate the optimal conditions for continuous production of the alpha-hydroxy acid. A mass of 1 kg [corrected] (R)-2-hydroxy-4-phenylbutyric acid was synthesized in a 220 ml enzyme membrane reactor over a period of 4 weeks. A mean space-time-yield of 165 g l-1 d-1 was achieved at low enzyme consumptions of 150 U kg-1 alpha-hydroxy acid for FDH and D-LDH.
（R）-2-羟基-4-苯基丁酸是制造血管紧张素转换酶抑制剂的中间体，可通过其相应的α-酮酸在酶膜反应器中进行酶促还原连续生产。来自表皮葡萄球菌的D-乳酸脱氢酶（D-LDH）被选为进行依赖于NADH的还原反应最合适的酶。甲酸脱氢酶（FDH）用于NADH再生。应用详细的动力学测量和耦合酶反应的数学模型来计算α-羟基酸连续生产的最佳条件。在220毫升酶膜反应器中，经过4周的时间合成了1千克[校正后]的（R）-2-羟基-4-苯基丁酸。在FDH和D-LDH的酶消耗低至150 U kg-1α-羟基酸的情况下，实现了165 g l-1 d-1的平均时空产率。
