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

doi:10.4014/jmb.1610.10079

QIBEBT-IR > 酶工程研究组

	Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from Streptomyces avermitilis
	Yao, Qiuping 1; Ma, Li2 ; Liu, Ling 1; Ikeda, Haruo 3; Fushinobu, Shinya 4; Li, Shengying 2; Xu, Lian-Hua 1
	2017-05-01
发表期刊	JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
卷号	27 期号:5 页码:956-964
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.
文章类型	Article
关键词	Compactin Cyp105d7 Pravastatin Streptomyces Avermitilis Hydroxylation
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
DOI	10.4014/jmb.1610.10079
关键词[WOS]	CHOLESTEROL-LOWERING DRUG ; BIOTRANSFORMATION SYSTEM ; CYTOCHROME P450SCA-2 ; PRAVASTATIN ; P450 ; MONOOXYGENASE ; BIOCONVERSION ; CARBOPHILUS ; DICLOFENAC ; EXPRESSION
收录类别	SCI
语种	英语
WOS研究方向	Biotechnology & Applied Microbiology ; Microbiology
项目资助者	National Natural Science Foundation(81402810)
WOS类目	Biotechnology & Applied Microbiology ; Microbiology
WOS记录号	WOS:000405680000011
引用统计
文献类型	期刊论文
条目标识符	http://ir.qibebt.ac.cn/handle/337004/9624
专题	酶工程研究组
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.