Cytochrome P450: taming a wild type enzyme.

Cytochrome P450: taming a wild type enzyme.
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DOI:
10.1016/j.copbio.2011.02.008
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发表时间:
2011-12
影响因子:
7.7
通讯作者:
Arnold, Frances H.
Arnold, Frances H.
中科院分区:
工程技术1区
文献类型:
--
作者:
Jung, Sang Taek;Lauchli, Ryan;Arnold, Frances H.

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细胞色素P450单加氧酶(P450)的蛋白质工程已经非常成功地产生有价值的非天然活性和性质,使这些强大的催化剂被用于药物代谢物的合成和青蒿素和紫杉醇的前体生产的生物合成途径。收集的经验表明,P450是高度“进化”的-它们对活性位点的突变特别稳健,并且容易接受新的底物并表现出新的选择性。它们在突变后适应新挑战的能力可能反映了它们活性位点的非极性性质以及它们高度的构象变异性。
Protein engineering of cytochrome P450 monooxygenases (P450s) has been very successful in generating valuable non-natural activities and properties, allowing these powerful catalysts to be used for the synthesis of drug metabolites and in biosynthetic pathways for the production of precursors of artemisinin and paclitaxel. Collected experience indicates that the P450s are highly 'evolvable'--they are particularly robust to mutation in their active sites and readily accept new substrates and exhibit new selectivities. Their ability to adapt to new challenges upon mutation may reflect the nonpolar nature of their active sites as well as their high degree of conformational variability.
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