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Membrane Permeability Selection Drove the Stereochemistry of Life

By Keith Cowing
Status Report
May 9, 2024
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Membrane Permeability Selection Drove the Stereochemistry of Life
Hexose sugar permeability through archaeal and hybrid membranes. Temporal dependence of average carboxyfluorescein (CF) fluorescence in the archaea-like G1PC phospholipid membrane (G1PC, filled symbols) and in the ‘hybrid’ phospholipid membrane (G3PC, open symbols) during the exposure to 1 mM of variant substrates delivered to the microfluidic coves. Mean (symbols) and standard deviation (error bars) were calculated from at least 10 single-vesicle measurements across three independent experiments. Data are processed and illustrated as described in Figure 1 legend. N is the number of single vesicles investigated for each substrate exposure and each type of vesicles. **: p-value < 0.01. Numerical values of CF fluorescence in individual vesicles for each lipid type during the delivery of each substrate are provided in S1 File and S2 File. --

Early in the evolution of life a proto-metabolic network was encapsulated within a membrane compartment. The permeability characteristics of the membrane determined several key functions of this network by determining which compounds could enter the compartment and which compounds could not.

One key feature of known life is the utilisation of right-handed D- ribose and deoxyribose sugars and left-handed L- amino acid stereochemical isomers (enantiomers), however, it is not clear why life adopted this specific chirality. We previously demonstrated that an archaeal and an intermediate membrane mimic, bearing a mixture of bacterial and archaeal lipid characteristics (a ‘hybrid’ membrane), display increased permeability compared to bacterial-like membranes.

Here, we investigate if these membranes can drive stereochemical selection on pentose sugars, hexose sugars and amino acids. Using permeability assays of homogenous unilamellar vesicles, we demonstrate that both membranes select for D- ribose and deoxyribose sugars while the hybrid membrane uniquely selects for a reduced alphabet of L- facing amino acids. This repertoire includes alanine, the plausible first L- amino acid utilised. We conclude such compartments could provide stereochemical compound selection thereby demonstrating a solution to the chirality problem during the evolution of life.

Membrane permeability selection drove the stereochemistry of life, (open access)


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