Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, Nijmegen AJ 6525, The Netherlands.
J Am Chem Soc. 2024 Mar 20;146(11):7839-7849. doi: 10.1021/jacs.4c01156. Epub 2024 Mar 6.
Biochemistry is dependent upon enzyme catalysts accelerating key reactions. At the origin of life, prebiotic chemistry must have incorporated catalytic reactions. While this would have yielded much needed amplification of certain reaction products, it would come at the possible cost of rapidly depleting the high energy molecules that acted as chemical fuels. Biochemistry solves this problem by combining kinetically stable and thermodynamically activated molecules (e.g., ATP) with enzyme catalysts. Here, we demonstrate a prebiotic phosphate transfer system involving an ATP analog (imidazole phosphate) and histidyl peptides, which function as organocatalytic enzyme analogs. We demonstrate that histidyl peptides catalyze phosphorylations via a phosphorylated histidyl intermediate. We integrate these histidyl-catalyzed phosphorylations into a complete prebiotic scenario whereby inorganic phosphate is incorporated into organic compounds though physicochemical wet-dry cycles. Our work demonstrates a plausible system for the catalyzed production of phosphorylated compounds on the early Earth and how organocatalytic peptides, as enzyme precursors, could have played an important role in this.
生物化学依赖于酶催化剂来加速关键反应。在生命起源时，前生物化学必须包含催化反应。虽然这将大大增加某些反应产物的产量，但也可能导致作为化学燃料的高能分子迅速耗尽。生物化学通过将动力学稳定和热力学激活的分子（例如 ATP）与酶催化剂结合来解决这个问题。在这里，我们展示了一个涉及 ATP 类似物（咪唑磷酸盐）和组氨酸肽的前生物磷酸盐转移系统，它们作为有机催化酶类似物发挥作用。我们证明组氨酸肽通过磷酸化组氨酸中间体催化磷酸化。我们将这些组氨酸催化的磷酸化整合到一个完整的前生物情景中，通过物理化学干湿循环将无机磷酸盐掺入有机化合物中。我们的工作证明了在早期地球上催化生成磷酸化化合物的一个合理系统，以及有机催化肽作为酶前体如何在这方面发挥重要作用。
