杰马克林
倍半萜
代谢工程
化学
生物化学
生物
植物
酶
作者
Yating Hu,Yongjin J. Zhou,Jichen Bao,Luqi Huang,Jens Nielsen,Anastasia Krivoruchko
出处
期刊:Journal of Industrial Microbiology & Biotechnology
[Oxford University Press]
日期:2017-07-01
卷期号:44 (7): 1065-1072
被引量:46
标识
DOI:10.1007/s10295-017-1934-z
摘要
Abstract Beta-elemene, a sesquiterpene and the major component of the medicinal herb Curcuma wenyujin, has antitumor activity against various types of cancer and could potentially serve as a potent antineoplastic drug. However, its current mode of production through extraction from plants has been inefficient and suffers from limited natural resources. Here, we engineered a yeast cell factory for the sustainable production of germacrene A, which can be transformed to beta-elemene by a one-step chemical reaction in vitro. Two heterologous germacrene A synthases (GASs) converting farnesyl pyrophosphate (FPP) to germacrene A were evaluated in yeast for their ability to produce germacrene A. Thereafter, several metabolic engineering strategies were used to improve the production level. Overexpression of truncated 3-hydroxyl-3-methylglutaryl-CoA reductase and fusion of FPP synthase with GAS, led to a sixfold increase in germacrene A production in shake-flask culture. Finally, 190.7 mg/l of germacrene A was achieved. The results reported in this study represent the highest titer of germacrene A reported to date. These results provide a basis for creating an efficient route for further industrial application re-placing the traditional extraction of beta-elemene from plant sources.
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