How Small Heterocycles Make a Reaction Network of Amino Acids and Nucleotides Efficient in Water

• Published in: Angewandte Chemie International Edition Vol. 58; no. 37; pp. 13087 - 13092
• Main Authors: Tremmel, Peter, Griesser, Helmut, Steiner, Ulrich E., Richert, Clemens
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 09.09.2019; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: Adenosine Monophosphate - chemistry; Adenosine Triphosphate - chemistry; Amino acids; Amino Acids - chemistry; AMP; Aqueous solutions; Carbodiimide; Carbodiimides - chemistry; Catalysis; Chemical bonds; Cyanamide - chemistry; Enzymes; Glycine; Heterocyclic Compounds - chemistry; Intermediates; Kinetics; Nucleotides; Nucleotides - chemistry; organocatalysis; Peptides; prebiotic chemistry; Pyrophosphates; Quantitative analysis; Rate constants; reaction networks; Ribonucleic acid; RNA; Substrates; Water - chemistry; organocatalysis; prebiotic chemistry; peptides; reaction networks; nucleotides
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201905427

Organisms use enzymes to ensure a flow of substrates through biosynthetic pathways. How the earliest form of life established biosynthetic networks and prevented hydrolysis of intermediates without enzymes is unclear. Organocatalysts may have played the role of enzymes. Quantitative analysis of reactions of adenosine 5’‐monophosphate and glycine that produce peptides, pyrophosphates, and RNA chains reveals that organocapture by heterocycles gives hydrolytically stabilized intermediates with balanced reactivity. We determined rate constants for 20 reactions in aqueous solutions containing a carbodiimide and measured product formation with cyanamide as a condensing agent. Organocapture favors reactions that are kinetically slow but productive, and networks, over single transformations. Heterocycles can increase the metabolic efficiency more than two‐fold, with up to 0.6 useful bonds per fuel molecule spent, boosting the efficiency of life‐like reaction systems in the absence of enzymes. Organocapture, in which a small heterocycle captures reactive intermediates by reacting with them, thereby suppressing their hydrolysis and modulating their reactivity, could have facilitated the formation of biosynthetic networks in the absence of enzymes on the early earth.