Optimizing Cytochrome P450 Reductase for Efficient Electron Transfer to Cytochrome P450 Monooxygenases

该研究计划的长期目标是使酶成为生产精细化学品和生物活性天然产品的高效生物催化剂。酶是一种大的细胞分子，在非常温和的反应条件下进行化学转化，控制精细(即通常只产生一种产品)。在许多情况下，这使它们成为传统化学催化剂的经济高效和可持续的替代品，传统化学催化剂通常使用高温和有毒金属。该研究计划的短期目标是提高一类名为细胞色素P450单加氧酶(P450)的酶的生物催化可行性。P450作用于广泛的化合物，并执行通过传统的“台式”化学合成无法复制的困难化学反应。然而，P450化学通常依赖于第二种酶--细胞色素P450还原酶(CPR)的电子转移，这在大规模工业过程中是一个非常低效的催化步骤。

The long-term goal of the research program is to engineer enzymes to be efficient biocatalysts for the production of fine chemicals and bioactive natural products. Enzymes, which are large cellular molecules, perform chemical transformations under very mild reaction conditions with exquisite control (i.e. one product typically is produced). In many cases, this makes them cost-effective and sustainable alternatives to traditional chemical catalysts, which often employ high temperatures and toxic metals. The short-term objective of the research program is to improve the biocatalytic feasability of a class of enzymes called cytochrome P450 monooxygenases (P450s). P450s act on a wide array of compounds and perform difficult chemical reactions that cannot be replicated through traditional “bench-top” chemical synthesis. However, P450 chemistry often relies on the transfer of electrons from a second enzyme, cytochrome P450 reductases (CPR), which is a very inefficient catalytic step in a scaled-up industrial process.