Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA.
Nature. 2016 Dec 14;540(7633):414-417. doi: 10.1038/nature20569.
Enzymes are ideal for use in asymmetric catalysis by the chemical industry, because their chemical compositions can be tailored to a specific substrate and selectivity pattern while providing efficiencies and selectivities that surpass those of classical synthetic methods. However, enzymes are limited to reactions that are found in nature and, as such, facilitate fewer types of transformation than do other forms of catalysis. Thus, a longstanding challenge in the field of biologically mediated catalysis has been to develop enzymes with new catalytic functions. Here we describe a method for achieving catalytic promiscuity that uses the photoexcited state of nicotinamide co-factors (molecules that assist enzyme-mediated catalysis). Under irradiation with visible light, the nicotinamide-dependent enzyme known as ketoreductase can be transformed from a carbonyl reductase into an initiator of radical species and a chiral source of hydrogen atoms. We demonstrate this new reactivity through a highly enantioselective radical dehalogenation of lactones-a challenging transformation for small-molecule catalysts. Mechanistic experiments support the theory that a radical species acts as an intermediate in this reaction, with NADH and NADPH (the reduced forms of nicotinamide adenine nucleotide and nicotinamide adenine dinucleotide phosphate, respectively) serving as both a photoreductant and the source of hydrogen atoms. To our knowledge, this method represents the first example of photo-induced enzyme promiscuity, and highlights the potential for accessing new reactivity from existing enzymes simply by using the excited states of common biological co-factors. This represents a departure from existing light-driven biocatalytic techniques, which are typically explored in the context of co-factor regeneration.
酶在化学工业的不对称催化中是理想的选择，因为它们的化学成分可以根据特定的底物和选择性模式进行调整，同时提供超越传统合成方法的效率和选择性。然而，酶仅限于自然界中存在的反应，因此，与其他形式的催化相比，能够促进的转化类型更少。因此，生物介导催化领域长期以来的挑战一直是开发具有新催化功能的酶。在这里，我们描述了一种实现催化混杂性的方法，该方法利用烟酰胺辅因子的光激发态（辅助酶介导催化的分子）。在可见光照射下，已知的依赖烟酰胺的酶——酮还原酶可以从羰基还原酶转变为自由基物种的引发剂和手性氢原子源。我们通过高度对映选择性的内酯的自由基脱卤反应来证明这种新的反应性，这是小分子催化剂的一个具有挑战性的转化。机制实验支持了这样一种理论，即自由基物种在该反应中作为中间体，NADH 和 NADPH（烟酰胺腺嘌呤二核苷酸和烟酰胺腺嘌呤二核苷酸磷酸的还原形式）既作为光还原剂又作为氢原子的来源。据我们所知，这种方法代表了光诱导酶混杂性的第一个例子，并且突出了通过简单地利用常见生物辅因子的激发态从现有酶中获取新反应性的潜力。这与现有的光驱动生物催化技术不同，后者通常在辅因子再生的背景下进行探索。
