Catalysts on Demand: Selective Oxidations by Laboratory-Evolved Cytochrome P450 BM3
Catalysts on Demand: Selective Oxidations by Laboratory-Evolved Cytochrome P450 BM3
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DOI：
10.2533/chimia.2009.309
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发表时间：
2009-01-01
期刊：
影响因子：
1.2
通讯作者：
Arnold, Frances H.
中科院分区：
文献类型：
--
作者：
Lewis, Jared C.;Arnold, Frances H.
非常需要使用大气氧选择性氧化C-H键的高效催化剂，以降低与传统氧化过程相关的经济和环境成本。我们使用定向进化方法来生成细菌细胞色素 P450 BM3 的变体，其催化多种非天然底物的羟基化和环氧化。这种脂肪酸羟化酶被转化为丙烷单加氧酶 (PMO)，能够以与天然底物上的 BM3 相当的速率对丙烷进行羟化。 PMO 进化谱系的变体显示出更宽的底物范围；这些成为一系列可以羟基化和衍生有机支架的酶的进化起点。这项工作展示了酶家族的单个成员如何通过进化轻松转化为有机合成催化剂的整个家族。
Efficient catalysts for selective oxidation of C-H bonds using atmospheric oxygen are highly desirable to decrease the economic and environmental costs associated with conventional oxidation processes. We have used methods of directed evolution to generate variants of bacterial cytochrome P450 BM3 that catalyze hydroxylation and epoxidation of a wide range of nonnative substrates. This fatty acid hydroxylase was converted to a propane monooxygenase (PMO) capable of hydroxylating propane at rates comparable to that of BM3 on its natural substrates. Variants along the PMO evolutionary lineage showed broadened substrate scope; these became the starting points for evolution of a wide array of enzymes that can hydroxylate and derivatize organic scaffolds. This work demonstrates how a single member of enzyme family is readily converted by evolution into a whole family of catalysts for organic synthesis.