Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions

Abstract

Numerous long-standing questions in origins-of-life research center on the history of biopolymers. For example, how and why did nature select the polypeptide backbone and proteinaceous side chains? Depsipeptides, containing both ester and amide linkages, have been proposed as ancestors of polypeptides. In this paper, we investigate cationic depsipeptides that form under mild dry-down reactions. We compare the oligomerization of various cationic amino acids, including the cationic proteinaceous amino acids (lysine, Lys; arginine, Arg; and histidine, His), along with nonproteinaceous analogs of Lys harboring fewer methylene groups in their side chains. These analogs, which have been discussed as potential prebiotic alternatives to Lys, are ornithine, 2,4-diaminobutyric acid, and 2,3-diaminopropionic acid (Orn, Dab, and Dpr). We observe that the proteinaceous amino acids condense more extensively than these nonproteinaceous amino acids. Orn and Dab readily cyclize into lactams, while Dab and Dpr condense less efficiently. Furthermore, the proteinaceous amino acids exhibit more selective oligomerization through their α-amines relative to their side-chain groups. This selectivity results in predominantly linear depsipeptides in which the amino acids are α-amine−linked, analogous to today’s proteins. These results suggest a chemical basis for the selection of Lys, Arg, and His over other cationic amino acids for incorporation into proto-proteins on the early Earth. Given that electrostatics are key elements of protein−RNA and protein−DNA interactions in extant life, we hypothesize that cationic side chains incorporated into proto-peptides, as reported in this study, served in a variety of functions with ancestral nucleic acid polymers in the early stages of life.

Primordial emergence of a nucleic acid binding protein via phase separation and statistical ornithine to arginine conversion

“…Thus, arginine may have first emerged as a spontaneous, chemical modification of ornithine sidechains in already synthesized polypeptides. The superior properties of arginine, in promoting coacervate formation, as well as dsDNA binding and folding, and the instability of ornithine esters, led to the takeover of arginine as a protein building block 23 .…”

“…Specifically, we explored the emergence of a nucleic acid-binding element. Early polypeptides, those emerging well before the last universal common ancestor (LUCA), likely interacted with polynucleic acids such as RNA [20][21][22][23] and possibly also with DNA 24 . However, early emergence of nucleic acids binding presents a conundrum.…”

The Future of Origin of Life Research: Bridging Decades-Old Divisions

“…Several have suggested fitness criteria for natural chemical selection, including the rate of entropy production [204] and other kinetic or thermodynamic features of chemical reactions, such as stoichiometric catalysis, autocatalysis, and cooperativity [205]. A specific example is the greater reactivity of proteinaceous amino acids when compared to their non-proteinaceous counterparts, which naturally selects from oligomers of the former [206]. At some point, most likely quite early during the development of prebiotic systems, genetic molecules did crystallize, and information storage became based on molecular recognition.…”

Polyesters as a Model System for Building Primitive Biologies from Non-Biological Prebiotic Chemistry

“…Although several studies suggest that biomolecules conferred a significant advantage to primitive systems resulting in their dominance in contemporary biochemistry [25][26][27] it does not Given the magnitude of prebiotic chemical diversity, the early environment likely included non-biomolecules along with biomolecules and quite possibly more of the former than the latter. However, relatively little effort has been expended towards understanding the identities or reactivity of the non-biomolecules generated in prebiotic syntheses [24], or the processes or novel chemical phenomena they might enable.…”

“…Although several studies suggest that biomolecules conferred a significant advantage to primitive systems resulting in their dominance in contemporary biochemistry [25][26][27] it does not necessarily follow that life was originally based on the same biomolecules. Indeed, it is known that biomolecules represent a minute fraction of the molecular diversity produced by prebiotic chemistry (as mentioned above) and this would tend to lower the probability that chemical bonds formed exclusively among biomolecules particularly in a one-pot prebiotic synthesis [3,24,28].…”