Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, CA 91125, USA.
Science. 2017 Oct 13;358(6360):215-218. doi: 10.1126/science.aao1482.
Catalytic anti-Markovnikov oxidation of alkene feedstocks could simplify synthetic routes to many important molecules and solve a long-standing challenge in chemistry. Here we report the engineering of a cytochrome P450 enzyme by directed evolution to catalyze metal-oxo-mediated anti-Markovnikov oxidation of styrenes with high efficiency. The enzyme uses dioxygen as the terminal oxidant and achieves selectivity for anti-Markovnikov oxidation over the kinetically favored alkene epoxidation by trapping high-energy intermediates and catalyzing an oxo transfer, including an enantioselective 1,2-hydride migration. The anti-Markovnikov oxygenase can be combined with other catalysts in synthetic metabolic pathways to access a variety of challenging anti-Markovnikov functionalization reactions.
烯烃原料的催化反马氏氧化可以简化许多重要分子的合成路线，并解决化学领域长期存在的一个挑战。在这里，我们通过定向进化工程改造细胞色素 P450 酶，以高效催化金属氧介导的反马氏氧化苯乙烯。该酶以分子氧为末端氧化剂，通过捕获高能中间体并催化氧转移，包括对映选择性 1,2-氢迁移，实现了对动力学有利的烯烃环氧化的反马氏选择性。反马氏加氧酶可以与合成代谢途径中的其他催化剂结合，以实现各种具有挑战性的反马氏功能化反应。
