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将大肠杆菌丙酮酸生成反应重编程以用于分支酸衍生物的生产。

Reprogramming Escherichia coli pyruvate-forming reaction towards chorismate derivatives production.

作者信息

Noda Shuhei, Mori Yutaro, Fujiwara Ryosuke, Shirai Tomokazu, Tanaka Tsutomu, Kondo Akihiko

机构信息

Center for Sustainable Resource Science, RIKEN, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.

Center for Sustainable Resource Science, RIKEN, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.

出版信息

Metab Eng. 2021 Sep;67:1-10. doi: 10.1016/j.ymben.2021.05.005. Epub 2021 May 24.

DOI:10.1016/j.ymben.2021.05.005
PMID:34044138
Abstract

Microbial metabolic pathway engineering is a potent strategy used worldwide to produce aromatic compounds. We drastically rewired the primary metabolic pathway of Escherichia coli to produce aromatics and their derivatives. The metabolic pathway of E. coli was compartmentalized into the production and energy modules. We focused on the pyruvate-forming reaction in the biosynthesis pathway of some compounds as the reaction connecting those modules. E. coli strains were engineered to show no growth unless pyruvate was synthesized along with the compounds of interest production. Production of salicylate and maleate was demonstrated to confirm our strategy's versatility. In maleate production, the production, yield against the theoretical yield, and production rate reached 12.0 g L, 67%, and up to fourfold compared to that in previous reports, respectively; these are the highest values of maleate production in microbes to our knowledge. The results reveal that our strategy strongly promotes the production of aromatics and their derivatives.

摘要

微生物代谢途径工程是一种在全球范围内用于生产芳香族化合物的有效策略。我们对大肠杆菌的初级代谢途径进行了大幅改造,以生产芳香族化合物及其衍生物。大肠杆菌的代谢途径被划分为生产模块和能量模块。我们将重点放在某些化合物生物合成途径中形成丙酮酸的反应上,因为该反应连接着这些模块。对大肠杆菌菌株进行工程改造,使其在不合成丙酮酸以及目标化合物的情况下无法生长。通过水杨酸和马来酸的生产证明了我们策略的通用性。在马来酸生产中,产量、相对于理论产量的产率以及生产率分别达到了12.0 g/L、67%,与之前的报道相比提高了四倍;据我们所知,这些是微生物中马来酸生产的最高值。结果表明,我们的策略有力地促进了芳香族化合物及其衍生物的生产。

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