Trotter Connor L, Era Yuta, Gordon Rory, Law Samantha, Switzer Christopher H, Wallace Stephen
Institute of Quantitative Biology, Biochemistry and Biotechnology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FF, U.K.
EaStCHEM School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, U.K.
JACS Au. 2025 Mar 29;5(4):2027-2032. doi: 10.1021/jacsau.5c00262. eCollection 2025 Apr 28.
Microbial metabolism is a diverse and sustainable source of synthetic reagents that can be programmed for controlled and high-level production via synthetic biology. However, despite the chemical diversity of metabolism, the chemical utility of metabolites, and the available tools to control metabolic chemistry, there remain few examples of the use of cellular metabolites directly for chemical synthesis. Herein, we report that diverse bacteria perform P=S bond formation (PhP to PhPS) via central sulfur metabolism and nonenzymatic chemistry , which can also be applied to affect microbial P=Se bond formation (PhPSe). To the best of our knowledge, this is the first biochemical and genetic investigation of P=S bond formation in a microbial cell and the first use of microbial metabolites for P=Se bond formation in chemical synthesis.
微生物代谢是合成试剂的一种多样且可持续的来源，可通过合成生物学进行编程以实现可控的高水平生产。然而，尽管代谢具有化学多样性、代谢物具有化学实用性以及有可用的工具来控制代谢化学，但直接利用细胞代谢物进行化学合成的例子仍然很少。在此，我们报道不同的细菌通过中心硫代谢和非酶化学过程进行P=S键的形成（从PhP到PhPS），这也可用于影响微生物中P=Se键的形成（PhPSe）。据我们所知，这是对微生物细胞中P=S键形成的首次生化和遗传学研究，也是微生物代谢物在化学合成中用于P=Se键形成的首次应用。
