Benzoxazoles are frequently found in synthetic pharmaceuticals and medicinally active natural products. To facilitate benzoxazole-based drug development, an eco-friendly and rapid platform for benzoxazole production is required. In this study, we have completed the biosynthesis of benzoxazoles in E. coli by coexpressing the minimal set of enzymes required for their biosynthesis. Moreover, by coupling this E. coli-based platform with precursor-directed biosynthesis, we have shown that the benzoxazole biosynthetic system is highly promiscuous in incorporating fluorine, chlorine, nitrile, picolinic, and alkyne functionalities into the scaffold. Our E. coli-based system thus paves the way for straightforward generation of novel benzoxazole analogues through future protein engineering and combinatorial biosynthesis.

中文翻译：

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基于大肠杆菌的生物合成平台扩展了天然苯并恶唑的结构多样性

苯并恶唑经常存在于合成药物和具有药用活性的天然产品中。为了促进基于苯并恶唑的药物开发，需要一个环保且快速的苯并恶唑生产平台。在这项研究中，我们通过共表达生物合成所需的最小酶集，完成了在大肠杆菌中苯并恶唑的生物合成。此外，通过将这种基于大肠杆菌的平台与前体导向的生物合成相结合，我们已经证明苯并恶唑生物合成系统在将氟、氯、腈、吡啶和炔官能团结合到支架中时是高度混杂的。我们的大肠杆菌因此，基于系统的系统为通过未来的蛋白质工程和组合生物合成直接生成新型苯并恶唑类似物铺平了道路。