Catalysts on Demand: Selective Oxidations by Laboratory-Evolved Cytochrome P450 BM3

  • Lewis J
  • Arnold F
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A review of the authors on research. Efficient catalysts for selective oxidn. of C-H bonds using atm. oxygen are highly desirable to decrease the economic and environmental costs assocd. with conventional oxidn. processes. We have used methods of directed evolution to generate variants of bacterial cytochrome P 450 BM3 that catalyze hydroxylation and epoxidn. of a wide range of non-native 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 org. scaffolds. This work demonstrates how a single member of enzyme family is readily converted by evolution into a whole family of catalysts for org. synthesis.

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  • Jared C. Lewis

  • Frances H. Arnold

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