Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin
文献类型： 外文期刊
作者： Wu, Junjun 1 ; Zhang, Xia 1 ; Zhu, Yingjie 1 ; Tan, Qinyu 1 ; He, Jiacheng 1 ; Dong, Mingsheng 1 ;
作者机构： 1.Nanjing Agr Univ, Coll Food Sci & Technol, Nanjing 210095, Jiangsu, Peoples R China
2.Jiangsu Acad Agr Sci, Inst Agroprod Proc, Nanjing 210095, Jiangsu, Peoples R China
期刊名称：SCIENTIFIC REPORTS （ 影响因子：4.379； 五年影响因子：5.133 ）
ISSN： 2045-2322
年卷期： 2017 年 7 卷
页码：
收录情况： SCI
摘要： Efficient biosynthesis of the plant polyphenol pinosylvin, which has numerous applications in nutraceuticals and pharmaceuticals, is necessary to make biological production economically viable. To this end, an efficient Escherichia coli platform for pinosylvin production was developed via a rational modular design approach. Initially, different candidate pathway enzymes were screened to construct de novo pinosylvin pathway directly from D-glucose. A comparative analysis of pathway intermediate pools identified that this initial construct led to the intermediate cinnamic acid accumulation. The pinosylvin synthetic pathway was then divided into two new modules separated at cinnamic acid. Combinatorial optimization of transcriptional and translational levels of these two modules resulted in a 16-fold increase in pinosylvin titer. To further improve the concentration of the limiting precursor malonyl-CoA, the malonyl-CoA synthesis module based on clustered regularly interspaced short palindromic repeats interference was assembled and optimized with other two modules. The final pinosylvin titer was improved to 281 mg/L, which was the highest pinosylvin titer even directly from D-glucose without any additional precursor supplementation. The rational modular design approach described here could bolster our capabilities in synthetic biology for value-added chemical production.
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