Length-Selective Synthesis of Acylglycerol-Phosphates through Energy-Dissipative Cycling

Abstract

The main aim of origins of life research is to find a plausible sequence of transitions from prebiotic chemistry to nascent biology. In this context, understanding how and when phospholipid membranes appeared on early Earth is critical to elucidating the prebiotic pathways that led to the emergence of primitive cells. Here we show that exposing glycerol-2-phosphate to acylating agents leads to the formation of a library of acylglycerol-phosphates. Medium-chain acylglycerol-phosphates were found to self-assemble into vesicles stable across a wide range of conditions and capable of retaining mono- and oligonucleotides. Starting with a mixture of activated carboxylic acids of different lengths, iterative cycling of acylation and hydrolysis steps allowed for the selection of longer-chain acylglycerol-phosphates. Our results suggest that a selection pathway based on energy-dissipative cycling could have driven the selective synthesis of phospholipids on early Earth.

Cyclophospholipids Increase Protocellular Stability to Metal Ions

“…Similarly, phosphorylation of this monoglyceride to give a cyclophospholipid increases the stability to pH and metal ions even further. Such incremental improvements with each discrete chemical step, presumably by energy-dissipative cycling, [48] suggest a path in which environmental selective pressures could lead to modern day lipids. The remaining step needed to convert the monoacyl cyclophospholipid to a contemporary diacyl phospholipid would greatly improve stability at the expense of the ability to acquire nutrients and grow and divide without protein machinery.…”

Provisioning the origin and early evolution of life

“…In our contribution to this ( Figure 2) [18][19][20][21]24], the pivotal importance of HCN is especially evidentevery carbon and nitrogen atom of the final set of products can ultimately derive from HCN. The set of products is directed by the inherent reactivity of HCN and intermediates derived therefrom under a geochemically plausible sequence of conditions.…”

“…To cut a long story short, organic chemists have pieced together reaction networks that make about half of the canonical amino acids, the pyrimidine and purine ribonucleotides and diacyl-glycerol-phosphate lipids [15][16][17][18][19][20][21][22][23][24]. On the basis of what is known to date, these chemists have made three conclusions that are germane to our argument:…”

Schrödinger'sWhat is Life?—The 75th Anniversary of a Book that Inspired Biology

“…Non‐enzymatic energy dissipative conversion of non‐assembling species into self‐assembling amphiphiles resulting in membrane structures was achieved in a more recent example (Scheme ). This particular process provides a spectacular insight into a possible prebiotic formation of phospholipid membranes …”