Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin

Abstract 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...

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Autores principales:	Junjun Wu, Xia Zhang, Yingjie Zhu, Qinyu Tan, Jiacheng He, Mingsheng Dong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0354266fb67b4c269c0103f9418943c5
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spelling	oai:doaj.org-article:0354266fb67b4c269c0103f9418943c52021-12-02T12:30:38ZRational modular design of metabolic network for efficient production of plant polyphenol pinosylvin10.1038/s41598-017-01700-92045-2322https://doaj.org/article/0354266fb67b4c269c0103f9418943c52017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01700-9https://doaj.org/toc/2045-2322Abstract 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.Junjun WuXia ZhangYingjie ZhuQinyu TanJiacheng HeMingsheng DongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Junjun Wu Xia Zhang Yingjie Zhu Qinyu Tan Jiacheng He Mingsheng Dong Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin
description	Abstract 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.
format	article
author	Junjun Wu Xia Zhang Yingjie Zhu Qinyu Tan Jiacheng He Mingsheng Dong
author_facet	Junjun Wu Xia Zhang Yingjie Zhu Qinyu Tan Jiacheng He Mingsheng Dong
author_sort	Junjun Wu
title	Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin
title_short	Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin
title_full	Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin
title_fullStr	Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin
title_full_unstemmed	Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin
title_sort	rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0354266fb67b4c269c0103f9418943c5
work_keys_str_mv	AT junjunwu rationalmodulardesignofmetabolicnetworkforefficientproductionofplantpolyphenolpinosylvin AT xiazhang rationalmodulardesignofmetabolicnetworkforefficientproductionofplantpolyphenolpinosylvin AT yingjiezhu rationalmodulardesignofmetabolicnetworkforefficientproductionofplantpolyphenolpinosylvin AT qinyutan rationalmodulardesignofmetabolicnetworkforefficientproductionofplantpolyphenolpinosylvin AT jiachenghe rationalmodulardesignofmetabolicnetworkforefficientproductionofplantpolyphenolpinosylvin AT mingshengdong rationalmodulardesignofmetabolicnetworkforefficientproductionofplantpolyphenolpinosylvin
_version_	1718394317082460160

Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin

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