Catalysis before Enzymes: Thiol-Rich Peptides as Molecular Diversity Providers on the Early Earth

Abstract

The multiplicity of simple molecules available on the primitive Earth probably made possible the development of extremely diverse prebiotic chemistry. The importance of thiols is widely recognized in the community studying the origin of life. De Duve’s “thioester world” has been considered a major contribution in this regard, where thioester bonds have high energies and thus can contribute to several chemical reactions. Herein, we propose specific models of thiols that exhibit unique activities toward several chemical reactions. Thanks to aminothiol and aminonitrile behaviors, we were able to obtain thiol-rich peptides with interesting catalytic activities leading to the formation of structurally diverse molecules. In a broader context, such chemistry could be introduced into systems chemistry scenarios in which it would be associated with the chemistry of nucleic acids or their precursors, as well as that of fatty acids.

Straightforward Creation of Possibly Prebiotic Complex Mixtures of Thiol-Rich Peptides

“…What we have tried to prove here is that starting from relatively simple molecules, complex mixtures can be obtained [25]. Thus, from the aminothiol-containing amidonitrile 11 (Cys-Met-CN) or 12 (Cys-Ala-CN), an array of compounds is observed after a few hours.…”

“…What we have tried to prove here is that starting from relatively simple molecules, complex mixtures can be obtained [25]. Thus, from the aminothiol-containing amidonitrile Some examples of the found linear polypeptides that contain thiazoline rings are shown in Table 3.…”

Thermodynamic Overview of Bioconjugation Reactions Pertinent to Lysine and Cysteine Peptide and Protein Residues

“…These acylations have been identified by their presence in many proteins, such as histones and mitochondrial proteins, which may alter their biological activity [189,[191][192][193]. It has also been suggested that these modifications may contribute to the aging process and have contributed to the development of simple metabolic pathways in primordial life [194][195][196][197][198][199][200]. Table 12 provides the calculated reaction thermodynamic values for the model reactions of these mentioned reactions, with compound 54 serving as a model for succinyl-CoA, yielding the acylated product 55 with methylamine serving as the lysine side chain; compound 56 serving as a model for glutaryl-CoA, yielding product 57; compound 58 serving as a surrogate of 3-hydroxy-3-methylglutaryl-CoA and producing 59; and compound 60 serving as a model for 3-methylglutaryl-CoA and yielding the N-acylated product 61.…”