Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from Streptomyces avermitilis

doi:10.4014/jmb.1610.10079

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	Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from Streptomyces avermitilis
	Yao, Qiuping 1; Ma, Li 2; Liu, Ling 1; Ikeda, Haruo 3; Fushinobu, Shinya 4; Li, Shengying 2; Xu, Lian-Hua 1
刊名	JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
	2017-05-01
卷号	27 期号:5 页码:956-964
关键词	Compactin Cyp105d7 Pravastatin Streptomyces Avermitilis Hydroxylation
DOI	10.4014/jmb.1610.10079
文献子类	Article
英文摘要	Compactin and pravastatin are competitive cholesterol biosynthesis inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase and belong to the statin drugs; however, the latter shows superior pharmacokinetic characteristics. Previously, we reported that the bacterial P450, CYP105D7, from Streptomyces avermitilis can catalyze the hydroxylation of 1-deoxypentalenic acid, diclofenac, and naringenin. Here, we demonstrate that CYP105D7 could also catalyze compactin hydroxylation in vitro. In the presence of both bacterial and cyanobacterial redox partner systems with an NADPH regeneration system, the reaction produced two hydroxylated products, including pravastatin (hydroxylated at the C6 position). The steady-state kinetic parameters were measured using the redox partners of putidaredoxin and its reductase. The K-m and k(cat) values for compactin were 39.1 +/- 8.8 mu M and 1.12 +/- 0.09 min(-1), respectively. The k(cat)/K-m value for compactin (0.029 min(-1)center dot mu M-1) was lower than that for diclofenac (0.114 min(-1)center dot mu M-1). Spectroscopic analysis showed that CYP105D7 binds to compactin with a K-d value of 17.5 +/- 3.6 mu M. Molecular docking analysis was performed to build a possible binding model of compactin. Comparisons of different substrates with CYP105D7 were conclusively illustrated for the first time.
WOS关键词	CHOLESTEROL-LOWERING DRUG ; BIOTRANSFORMATION SYSTEM ; CYTOCHROME P450SCA-2 ; PRAVASTATIN ; P450 ; MONOOXYGENASE ; BIOCONVERSION ; CARBOPHILUS ; DICLOFENAC ; EXPRESSION
WOS研究方向	Biotechnology & Applied Microbiology ; Microbiology
语种	英语
WOS记录号	WOS:000405680000011
资助机构	National Natural Science Foundation(81402810)
内容类型	期刊论文
源URL	[http://ir.qibebt.ac.cn/handle/337004/9624]
专题	青岛生物能源与过程研究所_酶工程团队
作者单位	1.Zhejiang Univ, Ocean Coll, Zhoushan 316021, Zhejiang, Peoples R China 2.Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Shandong Prov Key Lab Synthet Biol, Key Lab Biofuels, Qingdao 266101, Shandong, Peoples R China 3.Kitasato Univ, Kitasato Inst Life Sci, Sagamihara, Kanagawa 2520373, Japan 4.Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biotechnol, Tokyo 1138657, Japan
推荐引用方式 GB/T 7714	Yao, Qiuping,Ma, Li,Liu, Ling,et al. Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from Streptomyces avermitilis[J]. JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY,2017,27(5):956-964.
APA	Yao, Qiuping.,Ma, Li.,Liu, Ling.,Ikeda, Haruo.,Fushinobu, Shinya.,...&Xu, Lian-Hua.(2017).Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from Streptomyces avermitilis.JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY,27(5),956-964.
MLA	Yao, Qiuping,et al."Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from Streptomyces avermitilis".JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY 27.5(2017):956-964.