DICP OpenIR
学科主题物理化学
CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts
Guo, Juan1; Zhou, Yongjin J.2; Hillwigc, Matthew L.3; Shen, Ye1; Yang, Lei4,5; Wang, Yajun1; Zhang, Xianan1; Liu, Wujun2; Peters, Reuben J.3; Chen, Xiaoya4,5; Zhao, Zongbao K.2; Huang, Luqi1; Zhao ZB(赵宗保); Peters RJ; Huang LQ(黄璐琦)
关键词Phytoterpenoids Biosynthesis Gene Discovery Synthetic Pathway Metabolic Engineering
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2013-07-16
DOI10.1073/pnas.1218061110
110期:29页:12108-12113
收录类别SCI
合作性质
文章类型Article
部门归属18
项目归属1816
产权排名待补充
WOS标题词Science & Technology
资助者2,2 ; 2,2 ; 2,2 ; 2,2
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
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.
语种英语
资助者2,2 ; 2,2 ; 2,2 ; 2,2
原文出处查看原文
WOS记录号WOS:000322086100093
引用统计
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/119582
专题中国科学院大连化学物理研究所
通讯作者Zhao ZB(赵宗保); Peters RJ; Huang LQ(黄璐琦)
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.,...&黄璐琦.(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.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
2013UTNlU9MDfs.PDF(2118KB) 开放获取CC BY-NC-SA请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Guo, Juan]的文章
[Zhou, Yongjin J.]的文章
[Hillwigc, Matthew L.]的文章
百度学术
百度学术中相似的文章
[Guo, Juan]的文章
[Zhou, Yongjin J.]的文章
[Hillwigc, Matthew L.]的文章
必应学术
必应学术中相似的文章
[Guo, Juan]的文章
[Zhou, Yongjin J.]的文章
[Hillwigc, Matthew L.]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。