A Prebiotic Precursor to Life’s Phosphate Transfer System with an ATP Analog and Histidyl Peptide Organocatalysts

• Published in: Journal of the American Chemical Society Vol. 146; no. 11; pp. 7839 - 7849
• Main Authors: Maguire, Oliver R., Smokers, Iris B. A., Oosterom, Bob G., Zheliezniak, Alla, Huck, Wilhelm T. S.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20-03-2024
• Subjects: Adenosine Triphosphate; Catalysis; Origin of Life; Peptides; Phosphates
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.4c01156

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.