CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts

	CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts
	Guo, Juan 1; Zhou, Yongjin J.2; Hillwigc, Matthew L.3; Shen, Ye 1; Yang, Lei 4,5; Wang, Yajun 1; Zhang, Xianan 1; Liu, Wujun 2; Peters, Reuben J.3; Chen, Xiaoya 4,5
刊名	proceedings of the national academy of sciences of the united states of america
	2013-07-16
卷号	110 期号:29 页码:12108-12113
关键词	phytoterpenoids biosynthesis gene discovery synthetic pathway metabolic engineering
通讯作者	赵宗保 ; peters rj ; 黄璐琦
产权排序	待补充
合作状况	英
英文摘要	cytochrome p450 enzymes (cyps) play major roles in generating highly functionalized terpenoids, but identifying the exact biotransformation step(s) catalyzed by plant cyp in terpenoid biosynthesis is extremely challenging. tanshinones are abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components of the chinese medicinal herb danshen (salvia miltiorrhiza). whereas the diterpene synthases responsible for the conversion of (e,e,e)-geranylgeranyl diphosphate into the abietane miltiradiene, a potential precursor to tanshinones, have been recently described, molecular characterization of further transformation of miltiradiene remains unavailable. here we report stable-isotope labeling results that demonstrate the intermediacy of miltiradiene in tanshinone biosynthesis. we further use a next-generation sequencing approach to identify six candidate cyp genes being coregulated with the diterpene synthase genes in both the rhizome and danshen hairy roots, and demonstrate that one of these, cyp76ah1, catalyzes a unique four-electron oxidation cascade on miltiradiene to produce ferruginol both in vitro and in vivo. we then build upon the previous establishment of miltiradiene production in saccharomyces cerevisiae, with incorporation of cyp76ah1 and phyto-cyp reductase genes leading to heterologous production of ferruginol at 10.5 mg/l. as ferruginol has been found in many plants including danshen, the results and the approaches that were described here provide a solid foundation to further elucidate the biosynthesis of tanshinones and related diterpenoids. moreover, these results should facilitate the construction of microbial cell factories for the production of phytoterpenoids.
学科主题	物理化学
WOS标题词	science & technology
类目[WOS]	multidisciplinary sciences
研究领域[WOS]	science & technology - other topics
关键词[WOS]	gene-cluster ; salvia-miltiorrhiza ; terpenoid biosynthesis ; rice ; pathway ; cytochrome-p450 ; identification ; diterpenes ; diversification ; fosmidomycin
收录类别	SCI
资助信息	2，2
原文出处	12113
语种	英语
WOS记录号	WOS:000322086100093
公开日期	2014-09-11
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/119582]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
作者单位	1.China Acad Chinese Med Sci, Nat Resource Ctr Chinese Mat Med, Beijing 100700, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian 116023, Peoples R China 3.Iowa State Univ, Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Natl Key Lab Plant Mol Genet, Inst Plant Physiol & Ecol, Shanghai 200032, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Biol Sci, Plant Sci Res Ctr, Shanghai Chenshan Bot Garden, Shanghai 200032, Peoples R China
推荐引用方式 GB/T 7714	Guo, Juan,Zhou, Yongjin J.,Hillwigc, Matthew L.,et al. CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts[J]. proceedings of the national academy of sciences of the united states of america,2013,110(29):12108-12113.
APA	Guo, Juan.,Zhou, Yongjin J..,Hillwigc, Matthew L..,Shen, Ye.,Yang, Lei.,...&Huang, Luqi.(2013).CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts.proceedings of the national academy of sciences of the united states of america,110(29),12108-12113.
MLA	Guo, Juan,et al."CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts".proceedings of the national academy of sciences of the united states of america 110.29(2013):12108-12113.