Garrabou Xavier, Macdonald Duncan Stuart, Hilvert Donald
Laboratory of Organic Chemistry, ETH Zürich, 8093, Zürich, Switzerland.
Chemistry. 2017 May 2;23(25):6001-6003. doi: 10.1002/chem.201605757. Epub 2017 Jan 30.
The promiscuity of de novo designed enzymes provides a privileged platform for diverse abiological reactions. In this work, we report the first example of a nitroolefin synthase that catalyzes the Henry condensation between aromatic aldehydes and nitromethane. Significant catalytic activity was discovered in the computationally designed and evolved carboligase RA95.5-8, and mutations around the active site were shown to improve the reaction rate, demonstrating the potential to optimize the enzyme by directed evolution. This novel nitroolefin synthase could participate in complex biological cascades, whereby the highly tunable chemoselectivity could afford useful synthetic building blocks.
从头设计的酶的多功能性为各种非生物反应提供了一个特殊的平台。在这项工作中，我们报道了硝基烯烃合酶的首个实例，该酶催化芳香醛与硝基甲烷之间的亨利缩合反应。在通过计算设计和进化得到的碳连接酶RA95.5-8中发现了显著的催化活性，并且活性位点周围的突变被证明可以提高反应速率，这表明通过定向进化优化该酶的潜力。这种新型硝基烯烃合酶可以参与复杂的生物级联反应，凭借其高度可调的化学选择性能够提供有用的合成构件。
