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.

中文翻译：

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构建用于天然产物醋氨蝶呤的从头生物合成的大肠杆菌共培养物。

模块化共培养工程是一种复杂的天然产物生物合成的新兴方法。在这项研究中，分别构建了由两株和三株大肠杆菌组成的微生物共培养物，用于从头生物合成黄酮阿卡西汀，这是一种增值的天然化合物，具有简​​单的碳底物葡萄糖，具有许多已证明的生物活性。为此，异源生物合成途径分为不同的模块，每个模块都容纳在专用的大肠杆菌中功能表达菌株。优化组成菌株之间的接种率后，与单培养对照相比，工程共培养显示出4.83倍的产量提高。重要的是，在摇瓶中培养三株共培养物会在48小时后产生20.3 mg L ^-1 acacetin。据作者所知，这是关于异源微生物宿主中乙酰氨基乙酸从头生物合成的第一份报告。这项工作的结果证实了模块化共培养工程对于复杂类黄酮生物合成的有效性。