Chen Kai, Huang Xiongyi, Kan S B Jennifer, Zhang Ruijie K, Arnold Frances H
Division of Chemistry and Chemical Engineering 210-41, California Institute of Technology, Pasadena, CA 91125, USA.
Science. 2018 Apr 6;360(6384):71-75. doi: 10.1126/science.aar4239.
Small carbocycles are structurally rigid and possess high intrinsic energy due to their ring strain. These features lead to broad applications but also create challenges for their construction. We report the engineering of hemeproteins that catalyze the formation of chiral bicyclobutanes, one of the most strained four-membered systems, via successive carbene addition to unsaturated carbon-carbon bonds. Enzymes that produce cyclopropenes, putative intermediates to the bicyclobutanes, were also identified. These genetically encoded proteins are readily optimized by directed evolution, function in , and act on structurally diverse substrates with high efficiency and selectivity, providing an effective route to many chiral strained structures. This biotransformation is easily performed at preparative scale, and the resulting strained carbocycles can be derivatized, opening myriad potential applications.
小碳环结构刚性强，由于环张力而具有较高的内在能量。这些特性带来了广泛的应用，但也给它们的构建带来了挑战。我们报道了血红素蛋白的工程改造，该蛋白通过卡宾连续加成到不饱和碳 - 碳键上，催化手性双环丁烷的形成，双环丁烷是最具张力的四元体系之一。还鉴定出了产生环丙烯的酶，环丙烯是双环丁烷的假定中间体。这些基因编码的蛋白质很容易通过定向进化进行优化，在多种环境中发挥作用，并高效且选择性地作用于结构多样的底物，为许多手性张力结构提供了一条有效途径。这种生物转化很容易在制备规模上进行，并且所得的张力碳环可以进行衍生化，从而开启无数潜在应用。
