Genkwanin has various significant roles in nutrition, biomedicine, and pharmaceutical biology. Previously, this compound has been chiefly produced by plant-originated extraction or chemical synthesis. However, due to increasing concern and demand for safe food and environmental issues, the biotechnological production of genkwanin and other bioactive compounds based on safe, cheap, and renewable substrates has gained much interest. This paper described recombinant Escherichia coli-based co-culture engineering that was reconstructed for the de novo production of genkwanin from D-glucose. The artificial genkwanin biosynthetic chain was divided into two modules in which the upstream strain contained the genes for synthesizing p-coumaric acid from D-glucose. And, the downstream module contained a gene cluster that produced the precursor apigenin and the final product, genkwanin. The Box-Behnken design, a response surface methodology, was used to empirically model the production of genkwanin and optimize its productivity. As a result, the application of the designed co-culture improved the genkwanin production by 48.8 ± 1.3 mg/L or 1.7-fold compared to the mono-culture. In addition, the scale-up of genkwanin bioproduction by bioreactor resulted in 68.5 ± 1.9 mg/L at a 48 h time point. The combination of metabolic engineering and fermentation technology was therefore a very efficient and applicable approach to enhance the production of other bioactive compounds.

中文翻译：

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大肠杆菌共培养从头合成芫花素的代谢工程和优化

Genkwanin 在营养、生物医学和药物生物学中具有多种重要作用。此前，这种化合物主要通过植物提取或化学合成来生产。然而，由于对安全食品和环境问题的日益关注和需求，基于安全、廉价和可再生基质的芫花素和其他生物活性化合物的生物技术生产引起了人们的广泛兴趣。本文描述了基于重组大肠杆菌的共培养工程，该工程被重建用于从 D-葡萄糖从头生产芫花素。人工芫花素生物合成链分为两个模块，其中上游菌株含有从D-葡萄糖合成对香豆酸的基因。并且，下游模块包含产生前体芹菜素和最终产物芫花素的基因簇。Box-Behnken 设计是一种响应面方法，用于对芫花素的生产进行经验建模并优化其生产率。结果，与单一培养相比，设计的共培养的应用将芫花素产量提高了 48.8 ± 1.3 mg/L，即 1.7 倍。此外，生物反应器放大的芫花素生物生产在 48 小时时间点达到 68.5 ± 1.9 mg/L。因此，代谢工程和发酵技术的结合是提高其他生物活性化合物产量的非常有效且适用的方法。