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.
Highlights
Phospholipids are among the major components of all modern membranes.[1]
We investigated a similar scheme whereby iterative rounds of acylation and hydrolysis could efficiently allow for the selection of self-assembling amphiphiles through energy-dissipative cycling
Metal-based catalysis can be exploited to favor the hydrolytic ring-opening, which leads to the formation of the isomeric products glycerol-1-phosphate 6 and glycerol-2phosphate 7 (Figure S1). This suggests that other chemistry in addition to Fischer−Tropsch processes can contribute to the inventory of lipid building blocks on early Earth
Summary
Phospholipids are among the major components of all modern membranes.[1]. Their predominance, together with the fundamental role of compartmentalization, which allows the genetic and metabolic systems to cooperate and Darwinian evolution to occur, might suggest that such amphiphiles appeared at an early stage on the evolutionary timeline.[2]. We show that repeated cycles of acylation of the phospholipid precursor glycerol-2-phosphate, followed by hydrolysis of the products, lead to the selective accumulation of longer-chain amphiphiles capable of self-assembly into cell-like structures, suggesting a plausible pathway toward the emergence of biologically relevant membranes. We explored the ability of glycerol-2-phosphate 7 to undergo iterative rounds of competitive acylation and hydrolysis reactions, aiming to identify a selection process for selfassembling products from a heterogeneous library of amphiphiles (Figures S30−S35 and Table S3). We observed that the shorter-chain derivatives 10a−c hydrolyzed faster than the longer-chain analogue 10d, yielding 7 and the corresponding carboxylic acid 11a−d Encouraged by these results, we performed sequential rounds of acylation and hydrolysis wondering if longer-chain amphiphiles capable of membrane self-assembly might be selected (Figures 3 and S37−S38). In accordance with the cycling model proposed (Figure 3a), when 7 was subjected to multiple rounds of acylation with 8a−d and hydrolysis, the mixture became progressively enriched in the longer-chain amphiphiles (9d and 10d), at the expense of the shorter-chain species (9a−c and 10a−c), with concomitant formation of vesicles
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