Department of Biochemistry, School of Preclinical Medicine, Zunyi Medical University, No.6 West Xuefu Road, Xinpu District, Zunyi City, Guizhou Province, P. R. China.
Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Zunyi Medical University, No.6 West Xuefu Road, Xinpu District, Zunyi City, Guizhou Province, P. R. China.
Angew Chem Int Ed Engl. 2022 Sep 12;61(37):e202209272. doi: 10.1002/anie.202209272. Epub 2022 Aug 4.
Optically pure sulfoxides are noteworthy compounds applied in a wide range of industrial fields; however, the biocatalytic deracemization of racemic sulfoxides is challenging. Herein, a high-enantioselective methionine sulfoxide reductase A (MsrA) was combined with a low-enantioselective styrene monooxygenase (SMO) for the cyclic deracemization of sulfoxides. Enantiopure sulfoxides were obtained in >90 % yield and with >90 % enantiomeric excess (ee) through dynamic "selective reduction and non-selective oxidation" cycles. The cofactors of MsrA and SMO were subsequently regenerated by the cascade catalysis of three auxiliary enzymes through the consumption of low-cost D-glucose. Moreover, this "one-pot, one-step" cyclic deracemization strategy exhibited a wide substrate scope toward various aromatic, heteroaromatic, alkyl and thio-alkyl sulfoxides. This system proposed an efficient strategy for the green synthesis of chiral sulfoxide.
光学纯的亚砜是一类在众多工业领域都有应用的重要化合物；然而，外消旋亚砜的生物催化拆分却极具挑战性。在此，我们将高对映选择性的甲硫氨酸亚砜还原酶 A（MsrA）与低对映选择性的苯乙烯单加氧酶（SMO）结合起来，用于亚砜的循环外消旋化。通过动态的“选择性还原和非选择性氧化”循环，可以以＞90%的产率和＞90%的对映过量（ee）获得对映纯的亚砜。随后，通过三种辅助酶的级联催化，利用低成本的 D-葡萄糖消耗，再生 MsrA 和 SMO 的辅因子。此外，这种“一锅一步”的循环外消旋化策略对各种芳香族、杂芳香族、烷基和硫代烷基亚砜都表现出了较宽的底物范围。该体系为手性亚砜的绿色合成提供了一种有效的策略。
