Constructing E. coli Co‐Cultures for De Novo Biosynthesis of Natural Product Acacetin
Constructing E. coli Co‐Cultures for De Novo Biosynthesis of Natural Product Acacetin
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DOI：
10.1002/biot.202000131
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发表时间：
2020-06
影响因子：
4.7
通讯作者：
Xiaonan Wang;Alan Shao;Zhenghong Li;Lizelle Policarpio;Haoran Zhang
中科院分区：
文献类型：
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作者：
Xiaonan Wang;Alan Shao;Zhenghong Li;Lizelle Policarpio;Haoran Zhang
模块化共培养工程是复杂天然产物生物合成的一种新兴方法。在这项研究中，分别构建了由两种和三种大肠杆菌菌株组成的微生物共培养物，用于从简单的碳底物葡萄糖中重新合成黄酮类阿曲素，这是一种具有多种生物活性的增值天然化合物。为此，异种生物合成途径被分成不同的模块，每个模块都被安置在一个专门的大肠杆菌菌株中进行功能表达。优化各组成菌株的接种比例后，与单培养对照相比，工程共培养的产量提高了4.83倍。重要的是，三种菌株在摇瓶中共同培养48小时后产生20.3 mg L−1的阿卡星素。据作者所知，这是关于在异源微生物宿主中重新合成阿卡星素的第一篇报道。本研究结果证实了模块化共培养工程在复杂类黄酮生物合成中的有效性。
Modular co‐culture engineering is an emerging approach for biosynthesis of complex natural products. In this study, microbial co‐cultures composed of two and three Escherichia coli strains, respectively, are constructed for de novo biosynthesis of flavonoid acacetin, a value‐added natural compound possessing numerous demonstrated biological activities, from simple carbon substrate glucose. To this end, the heterologous biosynthetic pathway is divided into different modules, each of which is accommodated in a dedicated E. coli strain for functional expression. After the optimization of the inoculation ratio between the constituent strains, the engineered co‐cultures show a 4.83‐fold improvement in production comparing to the mono‐culture controls. Importantly, cultivation of the three‐strain co‐culture in shake flasks result in the production of 20.3 mg L−1 acacetin after 48 h. To the authors' knowledge, this is the first report on acacetin de novo biosynthesis in a heterologous microbial host. The results of this work confirm the effectiveness of modular co‐culture engineering for complex flavonoid biosynthesis.