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

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...

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Autores principales: Wu, Junjun, Zhang, Xia, Zhu, Yingjie, Tan, Qinyu, He, Jiacheng, Dong, Mingsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431097/
https://www.ncbi.nlm.nih.gov/pubmed/28469159
http://dx.doi.org/10.1038/s41598-017-01700-9
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author Wu, Junjun
Zhang, Xia
Zhu, Yingjie
Tan, Qinyu
He, Jiacheng
Dong, Mingsheng
author_facet Wu, Junjun
Zhang, Xia
Zhu, Yingjie
Tan, Qinyu
He, Jiacheng
Dong, Mingsheng
author_sort Wu, Junjun
collection PubMed
description 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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spelling pubmed-54310972017-05-16 Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin Wu, Junjun Zhang, Xia Zhu, Yingjie Tan, Qinyu He, Jiacheng Dong, Mingsheng Sci Rep Article 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. Nature Publishing Group UK 2017-05-03 /pmc/articles/PMC5431097/ /pubmed/28469159 http://dx.doi.org/10.1038/s41598-017-01700-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wu, Junjun
Zhang, Xia
Zhu, Yingjie
Tan, Qinyu
He, Jiacheng
Dong, Mingsheng
Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431097/
https://www.ncbi.nlm.nih.gov/pubmed/28469159
http://dx.doi.org/10.1038/s41598-017-01700-9
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