How molecular “handedness” emerged in early biology

Homochirality is still a research subject of great interest. This is the second research article in a few weeks that I came across (here is my blog post).

"... Research chemists, in two high-profile studies, have now proposed an elegant solution to this mystery, showing how this single-handedness or “homochirality” could have become established in biology. ...

Together, they suggest that the emergence of homochirality was due largely to a chemistry phenomenon called kinetic resolution, in which one chiral form becomes more abundant than another due to faster production and/or slower depletion. ...

“Origin of life” chemistry has been a busy field for much of the past century. Its practitioners have discovered dozens of key reactions that plausibly occurred on the early, “prebiotic” Earth to produce the first DNAs, RNAs, sugars, amino acids and other molecules that sustain life. Missing from this body of work, however, has been a plausible prebiotic theory for the emergence of homochirality. ...

The researchers specifically sought to reproduce homochirality in a central process in amino acid production called transamination, by using a relatively simple, plausibly prebiotic chemistry that excludes complex enzymes. ...
Ultimately, they discovered that when one type of amino acid in the starting pool of amino acids had even a moderate dominance of the left-handed form—as their other study made plausible—the faster reaction rate for left-handed-to-right-handed linkages preferentially depleted right-handed amino acids, leaving an ever-greater concentration of left-handed ones. Additionally, the left-right-left-right peptides had a stronger tendency to clump together and fall out of solution as solids. These kinetic resolution-related phenomena thus ended up yielding a surprisingly pure solution of almost fully left-handed peptides. ..."

From the significance and abstract 1:

"Significance

While much progress has been made in developing prebiotically plausible synthetic chemical routes to RNA, DNA, and peptides, as well as in prebiotic metabolic pathways, the question of the emergence of biological homochirality has often been left unexplored. Our work suggests that modern biological transamination may have evolved from a prebiotic half-reaction in reverse, effecting a kinetic resolution of racemic amino acids that preferentially leaves behind the proteinogenic amino acid enantiomer. This reaction joins several other recently reported prebiotically plausible kinetic resolutions that have been shown to produce enantioenriched sugar and amino acid building blocks. Kinetic resolution may be seen as an effective means of imparting stereochemical control that preceded and aided the development of highly selective asymmetric biocatalysts.

Abstract

The kinetic resolution of racemic amino acids mediated by dipeptides and pyridoxal provides a prebiotically plausible route to enantioenriched proteinogenic amino acids. The enzymatic transamination cycles that are key to modern biochemical formation of enantiopure amino acids may have evolved from this half of the reversible reaction couple. Kinetic resolution of racemic precursors emerges as a general route to enantioenrichment under prebiotic conditions."

From the abstract 2:

"The single chirality of biological molecules is a signature of life. Yet, rationalizing how single chirality emerged remains a challenging goal. Research has commonly focused on initial symmetry breaking and subsequent enantioenrichment of monomer building blocks—sugars and amino acids—that compose the genetic polymers RNA and DNA as well as peptides. If these building blocks are only partially enantioenriched, however, stalling of chain growth may occur, whimsically termed in the case of nucleic acids as “the problem of original syn”. Here, in studying a new prebiotically plausible route to proteinogenic peptides, we discovered that the reaction favours heterochiral ligation (that is, the ligation of L monomers with D monomers). Although this finding seems problematic for the prebiotic emergence of homochiral L-peptides, we demonstrate, paradoxically, that this heterochiral preference provides a mechanism for enantioenrichment in homochiral chains. Symmetry breaking, chiral amplification and chirality transfer processes occur for all reactants and products in multicomponent competitive reactions even when only one of the molecules in the complex mixture exhibits an imbalance in enantiomer concentrations (non-racemic). Solubility considerations rationalize further chemical purification and enhanced chiral amplification. Experimental data and kinetic modelling support this prebiotically plausible mechanism for the emergence of homochiral biological polymers."

How molecular “handedness” emerged in early biology | Scripps Research Scripps Research chemists fill a major gap in origin-of-life theories.

Prebiotic access to enantioenriched amino acids via peptide-mediated transamination reactions (no public access)

Symmetry breaking and chiral amplification in prebiotic ligation reactions (no public access)