Synthetic biology is becoming a conventional technique to maximize the production of interesting small molecule chemicals. However, it remains difficult to find the corresponding gene encoding enzymes for the biosynthesis of most new natural products or non-natural products. Many strategies, such as designing non-natural enzymes or artificial enzymes, have been tried to cross the boundary of microbial metabolism. Herein, PO₄³⁻ as a Brønsted acid catalyst is explored to catalyze the chemical reaction between azaphilones (a subgroup of fungi polyketides) and amines under mild conditions. We further demonstrate that the mild chemical reaction is biocompatible and can be directly interfaced with the microbial metabolism of azaphilones. The combination of chemo- and biosynthesis into a one-pot process in a simple way exhibits many advantages, such as diversifying natural azaphilone alkaloids, eliminating possible product inhibition or degradation, and acting as a novel strategy for sustainable chemistry.

中文翻译：

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磷酸盐催化反应与微生物代谢介导，以生产氮杂磷生物碱

合成生物学正在成为使感兴趣的小分子化学物质的产量最大化的常规技术。然而，仍然难以找到用于大多数新的天然产物或非天然产物的生物合成的相应的基因编码酶。已经尝试了许多策略，例如设计非天然酶或人造酶，以跨越微生物代谢的边界。在此，PO ₄ ^3-作为一种布朗斯台德酸催化剂，人们探索了其在温和条件下催化氮杂苯甲酮（真菌聚酮化合物的一个子类）与胺之间的化学反应的方法。我们进一步证明，温和的化学反应具有生物相容性，可以直接与氮杂苯甲酮的微生物代谢结合。化学合成和生物合成以一种简单的方式组合成一个罐的方法显示出许多优势，例如使天然的azaphilone生物碱多样化，消除可能的产物抑制或降解以及作为可持续化学的新策略。