微生物细胞色素P450酶及其对异源物质的代谢研究进展

Research progress in microbial cytochrome P450 and xenobiotic metabolism

细胞色素P450是一类广泛存在于动植物和微生物中的亚铁血红素-硫醇盐蛋白超家族,参与外源物质如药物、除草剂、杀虫剂和许多持久性难降解有机污染物等的生物氧化和降解.基于近年来文献综述P450酶的命名及分类、结构和催化机制,并总结微生物来源的P450酶在代谢和降解异源物质方面取得的研究进展.P450基因超家族主要依赖于氨基酸序列一致性进行统一命名和分类;P450酶结构虽较为保守,但其对底物的识别位点缺乏保守性,是构成其催化多样性的结构基础;细菌和真菌来源的部分P450酶能够代谢和降解异源物质,如多环芳烃、除草剂等,但效率较低,实际应用可能性较小.未来结合各种组学,需继续挖掘高效降解异源物质的P450酶资源,并对已有对异源物质有降解作用的P450酶进行蛋白分子改造,提高其活性并实现污染环境的生物修复.

Cytochrome P450（CYP450s） is a type of heme-mercaptide protein superfamily, which is distributed widely in animals, plants, and microorganisms. CYP450s can oxidize and degrade many exogenous compounds such as drugs, herbicides, pesticides, some persistent organic pollutants, and so on. Based on recent researches, this paper reviews the nomenclature, classification, structure, and catalytic mechanism of P450 enzymes, and summarizes the research progresses in the metabolism and biodegradation of xenobiotics using P450 enzymes from microorganisms. The nomenclature and classification of the P450 gene superfamily mainly rely on the similarities of amino acid sequences. Although the structures of P450 are conserved, their recognition sites towards to the substrates are variable. This is also the structural basis for the catalytic diversities of P450 enzymes. Few P450 enzymes from bacteria and fungi can metabolize and degrade xenobiotics such as polycyclic aromatic hydrocarbons, herbicides, and so on. However, these P450 enzymes are less likely be used in practical applications because of their low catalytic activities. In the future, more P450 enzymes with high degradable efficiencies towards xenobiotics are needed to be obtained using multiple omics tools or modifying the existing P450 enzymes, to achieve the bioremediation of the environment.