Biochemistry & Organic Chemistry

The Emergence of Chirality From Metabolism

By Keith Cowing
Status Report
q-bio.MN
May 12, 2025
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The Emergence of Chirality From Metabolism
A molecular-size dependent transition in the likelihood of achiral (A) and chiral (C) molecules within chemical space. (A) As heavy atoms are added to molecular graphs in an expanding chemical space, the total number of molecular configurations grows at least exponentially, and an abrupt transition marks where chiral centers become statistically more likely to be present — q-bio.MN

Molecular chirality is critical to biochemical function, but it is unknown when chiral selectivity first became important in the evolutionary transition from geochemistry to biochemistry during the emergence of life.

Here, we identify key transitions in the selection of chiral molecules in metabolic evolution, showing how achiral molecules (lacking chiral centers) may have given rise to specific and abundant chiral molecules in the elaboration of metabolic networks from geochemically available precursor molecules.

Simulated expansions of biosphere-scale metabolism suggest new hypotheses about the evolution of chiral molecules within biochemistry, including a prominent role for both achiral and chiral compounds as nucleation sites of early metabolic network growth, an increasing enrichment of molecules with more chiral centers as these networks expand, and conservation of broken chiral symmetries along reaction pathways as a general organizing principle.

We also find an unexpected enrichment in large, non-polymeric achiral molecules. Leveraging metabolic data of 40,023 genomes and metagenomes, we analyzed the statistics of chiral and achiral molecules in the large-scale organization of metabolism, revealing a chiral-enriched phase of network organization evidenced by system-size dependent chiral scaling laws that differ for individuals and ecosystems.

By uncovering how metabolic networks could lead to chiral selection, our findings open new avenues for bridging metabolism and genetics-first approaches to the origin of chirality, allowing tools for better timing of major transitions in molecular organization during the emergence of life, understanding the role of chirality in extant and synthetic metabolisms, and informing targets for chirality-based biosignatures.

John F. Malloy, Camerian Millsaps, Kamesh Narasimhan, Louie Slocombe, Cole Mathis, Leroy Cronin, Sara Imari Walker

Comments: 38 pages, 5 figures
Subjects: Molecular Networks (q-bio.MN)
Cite as: arXiv:2505.01056 [q-bio.MN] (or arXiv:2505.01056v1 [q-bio.MN] for this version)

https://doi.org/10.48550/arXiv.2505.01056
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Submission history
From: Sara Walker
[v1] Fri, 2 May 2025 07:04:57 UTC (15,867 KB)
https://arxiv.org/abs/2505.01056

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