{"title":"细胞色素P450催化的多种反应和类固醇激素的生物合成。","authors":"Keisuke Fujiyama, Tomoya Hino, Shingo Nagano","doi":"10.2142/biophysico.bppb-v19.0021","DOIUrl":null,"url":null,"abstract":"<p><p>Steroid hormones modulate numerous physiological processes in various higher organisms. Research on the physiology, biosynthesis, and metabolic degradation of steroid hormones is crucial for developing drugs, agrochemicals, and anthelmintics. Most steroid hormone biosynthetic pathways, excluding those in insects, have been elucidated, and the roles of several cytochrome P450s (CYPs, P450s), heme (iron protoporphyrin IX)-containing monooxygenases, have been identified. Specifically, P450s of the animal steroid hormone biosynthetic pathways and their three dimensional structures and reaction mechanisms have been extensively studied; however, the mechanisms of several uncommon P450 reactions involved in animal steroid hormone biosynthesis and structures and reaction mechanisms of various P450s involved in plant and insect steroid hormone biosynthesis remain unclear. Recently, we determined the crystal structure of P450 responsible for the first and rate-determining step in brassinosteroids biosynthesis and clarified the regio- and stereo-selectivity in the hydroxylation reaction mechanism. In this review, we have outlined the general catalytic cycle, reaction mechanism, and structure of P450s. Additionally, we have described the recent advances in research on the reaction mechanisms of steroid hormone biosynthesis-related P450s, some of which catalyze unusual P450 reactions including C-C bond cleavage reactions by utilizing either a heme-peroxo anion species or compound I as an active oxidizing species. This review article is an extended version of the Japanese article, Structure and mechanism of cytochrome P450s involved in steroid hormone biosynthesis, published in SEIBUTSU BUTSURI Vol. 61, p. 189-191 (2021).</p>","PeriodicalId":8976,"journal":{"name":"Biophysics and Physicobiology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/23/19_e190021.PMC9260165.pdf","citationCount":"2","resultStr":"{\"title\":\"Diverse reactions catalyzed by cytochrome P450 and biosynthesis of steroid hormone.\",\"authors\":\"Keisuke Fujiyama, Tomoya Hino, Shingo Nagano\",\"doi\":\"10.2142/biophysico.bppb-v19.0021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Steroid hormones modulate numerous physiological processes in various higher organisms. Research on the physiology, biosynthesis, and metabolic degradation of steroid hormones is crucial for developing drugs, agrochemicals, and anthelmintics. Most steroid hormone biosynthetic pathways, excluding those in insects, have been elucidated, and the roles of several cytochrome P450s (CYPs, P450s), heme (iron protoporphyrin IX)-containing monooxygenases, have been identified. Specifically, P450s of the animal steroid hormone biosynthetic pathways and their three dimensional structures and reaction mechanisms have been extensively studied; however, the mechanisms of several uncommon P450 reactions involved in animal steroid hormone biosynthesis and structures and reaction mechanisms of various P450s involved in plant and insect steroid hormone biosynthesis remain unclear. Recently, we determined the crystal structure of P450 responsible for the first and rate-determining step in brassinosteroids biosynthesis and clarified the regio- and stereo-selectivity in the hydroxylation reaction mechanism. In this review, we have outlined the general catalytic cycle, reaction mechanism, and structure of P450s. Additionally, we have described the recent advances in research on the reaction mechanisms of steroid hormone biosynthesis-related P450s, some of which catalyze unusual P450 reactions including C-C bond cleavage reactions by utilizing either a heme-peroxo anion species or compound I as an active oxidizing species. This review article is an extended version of the Japanese article, Structure and mechanism of cytochrome P450s involved in steroid hormone biosynthesis, published in SEIBUTSU BUTSURI Vol. 61, p. 189-191 (2021).</p>\",\"PeriodicalId\":8976,\"journal\":{\"name\":\"Biophysics and Physicobiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/23/19_e190021.PMC9260165.pdf\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biophysics and Physicobiology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2142/biophysico.bppb-v19.0021\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biophysics and Physicobiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2142/biophysico.bppb-v19.0021","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 2
摘要
类固醇激素在各种高等生物中调节许多生理过程。研究类固醇激素的生理、生物合成和代谢降解对开发药物、农用化学品和驱虫药至关重要。除昆虫外,大多数类固醇激素的生物合成途径已经被阐明,并且已经确定了几种细胞色素p450 (CYPs, p450),含血红素(铁原卟啉IX)的单加氧酶的作用。其中,动物类固醇激素生物合成途径的p450及其三维结构和反应机制得到了广泛的研究;然而,动物类固醇激素生物合成中几种不常见的P450反应的机制以及植物和昆虫类固醇激素生物合成中各种P450的结构和反应机制尚不清楚。最近,我们确定了油菜素内酯生物合成第一步和速率决定步骤P450的晶体结构,并阐明了羟基化反应机制中的区域选择性和立体选择性。本文综述了p450的催化循环、反应机理和结构。此外,我们还介绍了近年来类固醇激素生物合成相关的P450反应机制的研究进展,其中一些P450通过利用血红素-过氧阴离子或化合物I作为活性氧化物质来催化罕见的P450反应,包括C-C键裂解反应。这篇综述文章是日本文章《细胞色素p450参与类固醇激素生物合成的结构和机制》的扩展版,发表于SEIBUTSU BUTSURI Vol. 61, p. 189-191(2021)。
Diverse reactions catalyzed by cytochrome P450 and biosynthesis of steroid hormone.
Steroid hormones modulate numerous physiological processes in various higher organisms. Research on the physiology, biosynthesis, and metabolic degradation of steroid hormones is crucial for developing drugs, agrochemicals, and anthelmintics. Most steroid hormone biosynthetic pathways, excluding those in insects, have been elucidated, and the roles of several cytochrome P450s (CYPs, P450s), heme (iron protoporphyrin IX)-containing monooxygenases, have been identified. Specifically, P450s of the animal steroid hormone biosynthetic pathways and their three dimensional structures and reaction mechanisms have been extensively studied; however, the mechanisms of several uncommon P450 reactions involved in animal steroid hormone biosynthesis and structures and reaction mechanisms of various P450s involved in plant and insect steroid hormone biosynthesis remain unclear. Recently, we determined the crystal structure of P450 responsible for the first and rate-determining step in brassinosteroids biosynthesis and clarified the regio- and stereo-selectivity in the hydroxylation reaction mechanism. In this review, we have outlined the general catalytic cycle, reaction mechanism, and structure of P450s. Additionally, we have described the recent advances in research on the reaction mechanisms of steroid hormone biosynthesis-related P450s, some of which catalyze unusual P450 reactions including C-C bond cleavage reactions by utilizing either a heme-peroxo anion species or compound I as an active oxidizing species. This review article is an extended version of the Japanese article, Structure and mechanism of cytochrome P450s involved in steroid hormone biosynthesis, published in SEIBUTSU BUTSURI Vol. 61, p. 189-191 (2021).