DICP OpenIR
Subject Area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)
KeywordPhytoterpenoids Biosynthesis Gene Discovery Synthetic Pathway Metabolic Engineering
Source PublicationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2013-07-16
DOI10.1073/pnas.1218061110
Volume110Issue:29Pages:12108-12113
Indexed BySCI
Cooperation Status
SubtypeArticle
Department18
Funding Project1816
Contribution Rank待补充
WOS HeadingsScience & Technology
Funding Organization2,2 ; 2,2 ; 2,2 ; 2,2
WOS SubjectMultidisciplinary Sciences
WOS Research AreaScience & Technology - Other Topics
WOS KeywordGENE-CLUSTER ; SALVIA-MILTIORRHIZA ; TERPENOID BIOSYNTHESIS ; RICE ; PATHWAY ; CYTOCHROME-P450 ; IDENTIFICATION ; DITERPENES ; DIVERSIFICATION ; FOSMIDOMYCIN
AbstractCytochrome 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.
Language英语
Funding Organization2,2 ; 2,2 ; 2,2 ; 2,2
URL查看原文
WOS IDWOS:000322086100093
Citation statistics
Cited Times:123[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/119582
Collection中国科学院大连化学物理研究所
Corresponding AuthorZhao ZB(赵宗保); Peters RJ; Huang LQ(黄璐琦)
Affiliation1.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
Recommended Citation
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.
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