Enabling Heterologous Synthesis of Lupulones in the Yeast Saccharomyces cerevisiae
文献类型：期刊论文
| 作者 | Guo, Xiaojia1,2; Shen, Hongwei1; Liu, Yuxue1,2; Wang, Qian1; Wang, Xueying1; Peng, Chang1; Liu, Wujun1; Zhao, Zongbao K.1 |
| 刊名 | APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
 |
| 出版日期 | 2019-07-01 |
| 卷号 | 188期号:3页码:787-797 |
| 关键词 | Chemical genetics Lupulones Metabolic engineering Mevalonate pathway Saccharomyces cerevisiae |
| ISSN号 | 0273-2289 |
| DOI | 10.1007/s12010-019-02957-8 |
| 通讯作者 | Zhao, Zongbao K.(zhaozb@dicp.ac.cn) |
| 英文摘要 | Lupulones, naturally produced by glandular trichomes of hop (Humulus lupulus), are prenylated phloroglucinol derivatives that contribute the bitter flavor of beer and demonstrate antimicrobial and anticancer activities. It is appealing to develop microbial cell factories such that lupulones may be produced via fermentation technology in lieu of extraction from limited plant resources. In this study, the yeast Saccharomyces cerevisiae transformants harboring a synthetic lupulone pathway that consisted of five genes from hop were constructed. The transformants accumulated several precursors but failed to accumulate lupulones. Overexpression of 3-hydroxy-3-methyl glutaryl co-enzyme A reductase, the key enzyme in precursor formation in the mevalonate pathway, also failed to achieve a detectable level of lupulones. To decrease the consumption of the precursors, the ergosterol biosynthesis pathway was chemically downregulated by a small molecule ketoconazole, leading to successful production of lupulones. Our study demonstrated a combination of molecular biology and chemical biology to regulate the metabolism for heterologous production of lupulones. The strategy may be valuable for future engineering microbial process for other prenylated natural products. |
| WOS关键词 | SQUALENE SYNTHASE INHIBITORS ; IN-VITRO ; HUMULUS-LUPULUS ; ACID ; CHAIN ; BIOSYNTHESIS ; METABOLISM ; EFFICIENCY ; CATALYZES ; ER-119884 |
| 资助项目 | National Natural Science Foundation of China[21721004] ; National Natural Science Foundation of China[51561145014] ; Dalian Institute of Chemical Physics, CAS ; DICP[ZZBS201605] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000471851400013 |
| 出版者 | SPRINGER |
| 资助机构 | National Natural Science Foundation of China ; National Natural Science Foundation of China ; Dalian Institute of Chemical Physics, CAS ; Dalian Institute of Chemical Physics, CAS ; DICP ; DICP ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Dalian Institute of Chemical Physics, CAS ; Dalian Institute of Chemical Physics, CAS ; DICP ; DICP ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Dalian Institute of Chemical Physics, CAS ; Dalian Institute of Chemical Physics, CAS ; DICP ; DICP ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Dalian Institute of Chemical Physics, CAS ; Dalian Institute of Chemical Physics, CAS ; DICP ; DICP |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/175868]  |
| 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 |
| 通讯作者 | Zhao, Zongbao K. |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian 116023, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, Xiaojia,Shen, Hongwei,Liu, Yuxue,et al. Enabling Heterologous Synthesis of Lupulones in the Yeast Saccharomyces cerevisiae[J]. APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY,2019,188(3):787-797. |
| APA | Guo, Xiaojia.,Shen, Hongwei.,Liu, Yuxue.,Wang, Qian.,Wang, Xueying.,...&Zhao, Zongbao K..(2019).Enabling Heterologous Synthesis of Lupulones in the Yeast Saccharomyces cerevisiae.APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY,188(3),787-797. |
| MLA | Guo, Xiaojia,et al."Enabling Heterologous Synthesis of Lupulones in the Yeast Saccharomyces cerevisiae".APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY 188.3(2019):787-797. |
入库方式： OAI收割
来源：大连化学物理研究所
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