Ester‐Mediated Amide Bond Formation Driven by Wet–Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth

Forsythe, Jay G.; Yu, Shengsheng; Mamajanov, Irena; Grover, Martha A.; Krishnamurthy, Ramanarayanan; Fernández, Facundo M.; Hud, Nicholas V.

doi:10.1002/ange.201503792

Cited by 68 publications

(54 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Or, in the experiments of Kanavarioti et al (36), polymers of oligouridylates are found up to lengths of 11 bases long, with an average length of 4 after samples of phosphoimidazolide-activated uridine were frozen in the presence of metal ions in dilute solutions. Similar results are found in other polymers: a prebiotically plausible mechanism produces oligomers having a combination of ester and amide bonds up to length 14 (38).…”

Section: "Flory Length Problem": Polymerization Processes Produce Mossupporting

confidence: 85%

See 1 more Smart Citation

Foldamer hypothesis for the growth and sequence differentiation of prebiotic polymers

Guseva

Zuckermann

Dill

2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

It is not known how life originated. It is thought that prebiotic processes were able to synthesize short random polymers. However, then, how do short-chain molecules spontaneously grow longer? Also, how would random chains grow more informational and become autocatalytic (i.e., increasing their own concentrations)? We study the folding and binding of random sequences of hydrophobic (H) and polar (P) monomers in a computational model. We find that even short hydrophobic polar (HP) chains can collapse into relatively compact structures, exposing hydrophobic surfaces. In this way, they act as primitive versions of today's protein catalysts, elongating other such HP polymers as ribosomes would now do. Such foldamer catalysts are shown to form an autocatalytic set, through which short chains grow into longer chains that have particular sequences. An attractive feature of this model is that it does not overconverge to a single solution; it gives ensembles that could further evolve under selection. This mechanism describes how specific sequences and conformations could contribute to the chemistry-to-biology (CTB) transition.origin of life | HP model | biopolymers | autocatalytic sets A mong the most mysterious processes in chemistry is how the spontaneous transition occurred more than 3 billion years ago from a soup of prebiotic molecules to living cells. What was the mechanism of the chemistry-to-biology (CTB) transition? In this paper, we develop a model to explore how prebiotic polymerization processes might have produced long chains of proteinlike or nucleic acid-like molecules (1, 2). What polymerization processes are autocatalytic? How could they have produced long chains? Also, how might random chain sequences have become informational and self-serving? Our questions here are about physical spontaneous mechanisms, not about specific monomer or polymer chemistries. CTB Requires an Autocatalytic ProcessEarly on, it was recognized that the transition from simple chemistry to self-supporting biological behavior requires autocatalysis (i.e., some form of positive feedback or bootstrapping, in which the concentrations of some molecules become amplified and selfsustaining relative to other molecules) (3-8). That work has led to the idea of an autocatalytic set, a collection of entities in which any one entity can catalyze another.We first review some of the key results. A class of models called Graded Autocatalysis Replication Domain (GARD) (9-11) predicts that artificial autocatalytic chemical kinetic networks can lead to self-replication, with a corresponding amplification of some chemicals over others. Such systems display some degree of inheritance and adaptability. GARD model is a subset of metabolism first models, which envision that small molecule chemical processes precede information transfer and precede the first biopolymers. Focusing on polymers, Wu and Higgs (12) developed a model of RNA chain-length autocatalysis. They envision that some of the RNA chains can spontaneously serve as polymerase ribozymes, l...

show abstract

Section: "Flory Length Problem": Polymerization Processes Produce Mossupporting

confidence: 85%

“…Longer chains can sometimes result through adsorption to clays (31,32) or minerals (33,34), from evaporation from tidal pools (35), from concentration in ice through eutectic melts (36), or from freezing (37) or temperature cycling. Even so, the chainlength extensions are modest (38).…”

Section: "Flory Length Problem": Polymerization Processes Produce Mosmentioning

confidence: 99%

Foldamer hypothesis for the growth and sequence differentiation of prebiotic polymers

Guseva

Zuckermann

Dill

2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Models of mutualism and cooperative effects in autocatalytic sets, on quasi-species, the protein world and the RNA world (see for example, [3][4][5][6]) all assume tacitly the homochirality of the implied species. The origin of biological homochirality is thus considered as a separate and disjoint event: the formation of enantiomerically pure polymers is assumed to occur by starting from enantiomerically pure mixtures of their monomers.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous mirror symmetry breaking and origin of biological homochirality

Ribó

Hochberg

Crusats

et al. 2017

J. R. Soc. Interface.

View full text Add to dashboard Cite

Recent reports on both theoretical simulations and on the physical chemistry basis of spontaneous mirror symmetry breaking (SMSB), that is, asymmetric synthesis in the absence of any chiral polarizations other than those arising from the chiral recognition between enantiomers, strongly suggest that the same nonlinear dynamics acting during the crucial stages of abiotic chemical evolution leading to the formation and selection of instructed polymers and replicators, would have led to the homochirality of instructed polymers. We review, in the first instance, which reaction networks lead to the nonlinear kinetics necessary for SMSB, and the thermodynamic features of the systems where this potentiality may be realized. This could aid not only in the understanding of SMSB, but also the design of reliable scenarios in abiotic evolution where biological homochirality could have taken place. Furthermore, when the emergence of biological chirality is assumed to occur during the stages of chemical evolution leading to the selection of polymeric species, one may hypothesize on a tandem track of the decrease of symmetry order towards biological homochirality, and the transition from the simple chemistry of astrophysical scenarios to the complexity of systems chemistry yielding Darwinian evolution.

show abstract

“…We recently introduced a model prebiotic pathway for peptide formation based on ester-amide exchange reactions between α-amino acids and α-hydroxy acids (12), amino acid structural analogs found in meteorites and model prebiotic reactions (13,14) ( Fig. 1A).…”

mentioning

confidence: 99%

“…Three prebiotic amino acids, glycine (G), L-alanine (A), and L-leucine (L), were mixed with one hydroxy acid: glycolic acid (g), L-lactic acid (a), or L-malic acid (d). Each mixture contained one hydroxy acid and three amino acids (g+G+A+L, a+G+A+L, and d+G+A+L) and was subjected to one, two, or four 85°C-dry/65°C-wet cycles chosen to model a daily evaporating pool environment on the early Earth (12). The resulting nine depsipeptide libraries were examined by ultraperformance liquid chromatography -ion mobility-tandem mass spectrometry (UPLC-IM-MS/MS) in data-dependent acquisition (DDA) mode.…”

mentioning

confidence: 99%

Surveying the sequence diversity of model prebiotic peptides by mass spectrometry

Forsythe

Petrov

Millar

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

The rise of peptides with secondary structures and functions would have been a key step in the chemical evolution which led to life. As with modern biology, amino acid sequence would have been a primary determinant of peptide structure and activity in an originsof-life scenario. It is a commonly held hypothesis that unique functional sequences would have emerged from a diverse soup of proto-peptides, yet there is a lack of experimental data in support of this. Whereas the majority of studies in the field focus on peptides containing only one or two types of amino acids, here we used modern mass spectrometry (MS)-based techniques to separate and sequence de novo proto-peptides containing broader combinations of prebiotically plausible monomers. Using a dry-wet environmental cycling protocol, hundreds of proto-peptide sequences were formed over a mere 4 d of reaction. Sequence homology diagrams were constructed to compare experimental and theoretical sequence spaces of tetrameric proto-peptides. MS-based analyses such as this will be increasingly necessary as origins-of-life researchers move toward systems-level investigations of prebiotic chemistry. . Soon after, Fox and Harada began to explore the formation of peptides from amino acids via condensation at high temperatures (2). These reactions were facilitated by proportionally higher concentrations of amino acids with acidic side chains (e.g., aspartic acid, D) and resulted in the production of "proteinoids," condensation products containing covalent cross-links not found in coded proteins. In their 1960 manuscript, Fox and Harada speculated about the diversity of proteinoid sequences, yet conceded that "a complete answer to the question of whether the amino acid residues are distributed in a random or other arrangement may require a complete assignment of residues in one molecular species," a task beyond the analytical capabilities of the time (3).In subsequent years, the proteinoid concept was displaced by the hypothesis that either RNA or proto-RNA gave rise to life (4-6). Nevertheless, to this day, condensation reactions of amino acids are thought to have played a key role in a potentially symbiotic proto-nucleic acid and proto-peptide world (7,8). Peptide condensation studies at temperatures lower than those of Fox and Harada, or with the aid of chemical agents, confirmed that abiotic production of peptides was indeed possible, but chain lengths were generally limited to dimers and trimers with low yields (9). In recent studies, this length barrier has been surpassed, and certain proto-peptides have been shown to form aggregate structures (10, 11). Nevertheless, the majority of proto-peptide studies have been limited in scope, typically containing only one or two types of amino acid monomer.We recently introduced a model prebiotic pathway for peptide formation based on ester-amide exchange reactions between α-amino acids and α-hydroxy acids (12), amino acid structural analogs found in meteorites and model prebiotic reactions (13, 14) (Fig. 1A). Subjecting ...

show abstract

Ester‐Mediated Amide Bond Formation Driven by Wet–Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth

Cited by 68 publications

References 32 publications

Foldamer hypothesis for the growth and sequence differentiation of prebiotic polymers

Foldamer hypothesis for the growth and sequence differentiation of prebiotic polymers

Spontaneous mirror symmetry breaking and origin of biological homochirality

Surveying the sequence diversity of model prebiotic peptides by mass spectrometry

Contact Info

Product

Resources

About