Stereoselective synthesis of phenylpropane 1,2-diols from (S)-2-hydroxypropiophenone by NADH-dependent oxidoreductases

Abstract

In this study, alcohol dehydrogenase (EC 1.1.1.2) from Lactobacillus brevis and glycerol dehydrogenase (EC 1.1.1.6) from Cellulomonas sp. were used for the reduction of (S)-2-hydroxypropiophenone to (1S, 2S)- and (1R, 2S)-1-phenylpropane-1,2-diol, respectively. As both dehydrogenases belong to NADH-dependent oxidoreductases, due to high coenzyme cost, the possibility of NADH regeneration was considered by using the enzyme-coupled regeneration system with formate dehydrogenase (EC 1.2.1.2) from Candida boidinii. All three enzymes were kinetically characterized and the kinetics of all reactions were determined using the method of initial rates. Based on kinetic results mathematical models were developed for the synthesis of both phenylpropane 1,2-diols for the systems with and without coenzyme regeneration and were validated in a batch reactor. The equilibrium conversions of 60% and 33% were achieved without coenzyme regeneration using alcohol and glycerol dehydrogenase, respectively, while with coenzyme regeneration a complete (S)-2-hydroxypropiophenone conversion was achieved with both enzymes.