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Permeability selection of biologically relevant membranes matches the stereochemistry of life on Earth

Abstract:
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 utilization of right-handed d-ribose and d-deoxyribose sugars and left-handed l-amino acid stereochemical isomers (enantiomers); however, it is not clear why life adopted this specific chirality. Generally, archaea have l-phospholipid membrane chemistries and bacteria and eukaryotes have d-phospholipid membrane chemistries. We previously demonstrated that an l-archaeal and a d-intermediate membrane mimic, bearing a mixture of bacterial and archaeal lipid characteristics (a 'hybrid' membrane), displayed increased permeability for several key compounds 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 d-deoxyribose sugars while the hybrid membrane uniquely selects for a reduced alphabet of l-amino acids. This repertoire includes alanine, the plausible first l-amino acid utilized. We conclude such compartments could provide stereochemical compound selection matching those used by the core metabolism of life.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1371/journal.pbio.3003155

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Institution:
University of Oxford
Division:
MPLS
Department:
Biology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Biology
Role:
Author
ORCID:
0000-0003-3669-7463


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Funder identifier:
https://ror.org/03wnrjx87
Grant:
URF\R\191005


Publisher:
Public Library of Science
Journal:
PLoS Biology More from this journal
Volume:
23
Issue:
5
Article number:
e3003155
Place of publication:
United States
Publication date:
2025-05-20
Acceptance date:
2025-04-07
DOI:
EISSN:
1545-7885
ISSN:
1544-9173


Language:
English
Pubs id:
2125731
Local pid:
pubs:2125731
Deposit date:
2025-05-24
ARK identifier:

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