Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, China.
Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, China.
Angew Chem Int Ed Engl. 2022 Sep 12;61(37):e202205790. doi: 10.1002/anie.202205790. Epub 2022 Aug 3.
We report the discovery of an unusual halohydrin dehalogenase, HHDHamb, that can work under relatively low acidic conditions and extremely low temperatures for the bio-nitration of epoxides using nitrite as a nitrating agent. The bio-nitration strategy exhibits high chemo-, regio-, and enantioselectivity, catalyzing the kinetic resolution of various epoxides to enantiopure β-nitroalcohols with nitro-bearing stereocenters in up to 41 % isolated yield and >99 % enantiomeric excess (ee). Additionally, the bio-nitration method displays a high reaction efficiency and can be performed on a gram scale. We also solved the crystal structure of HHDHamb to understand the possible structural determinants of chemoselectivity control in the bio-nitration reaction.
我们报告了一种不寻常的卤醇脱卤酶 HHDHamb 的发现，它可以在相对较低的酸性条件和极低的温度下工作，使用亚硝酸作为硝化剂，对环氧化物进行生物硝化。该生物硝化策略表现出高的化学选择性、区域选择性和对映选择性，催化各种环氧化物的动力学拆分，以高达 41%的分离产率和>99%的对映体过量（ee）得到具有硝基手性中心的对映纯β-硝基醇。此外，生物硝化方法显示出高的反应效率，可以在克级规模上进行。我们还解析了 HHDHamb 的晶体结构，以了解生物硝化反应中化学选择性控制的可能结构决定因素。
