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dc.contributor.authorPiedrafita, Gabriel
dc.contributor.authorVarma, Sreejith J
dc.contributor.authorCastro, Cecilia
dc.contributor.authorMessner, Christoph B
dc.contributor.authorSzyrwiel, Lukasz
dc.contributor.authorGriffin, Julian L
dc.contributor.authorRalser, Markus
dc.date.accessioned2022-01-05T10:48:13Z
dc.date.available2022-01-05T10:48:13Z
dc.date.issued2021-12
dc.date.submitted2021-01-30
dc.identifier.issn1544-9173
dc.identifier.otherpbiology-d-21-00293
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331996
dc.description.abstractThe structure of the metabolic network is highly conserved, but we know little about its evolutionary origins. Key for explaining the early evolution of metabolism is solving a chicken-egg dilemma, which describes that enzymes are made from the very same molecules they produce. The recent discovery of several nonenzymatic reaction sequences that topologically resemble central metabolism has provided experimental support for a "metabolism first" theory, in which at least part of the extant metabolic network emerged on the basis of nonenzymatic reactions. But how could evolution kick-start on the basis of a metal catalyzed reaction sequence, and how could the structure of nonenzymatic reaction sequences be imprinted on the metabolic network to remain conserved for billions of years? We performed an in vitro screening where we add the simplest components of metabolic enzymes, proteinogenic amino acids, to a nonenzymatic, iron-driven reaction network that resembles glycolysis and the pentose phosphate pathway (PPP). We observe that the presence of the amino acids enhanced several of the nonenzymatic reactions. Particular attention was triggered by a reaction that resembles a rate-limiting step in the oxidative PPP. A prebiotically available, proteinogenic amino acid cysteine accelerated the formation of RNA nucleoside precursor ribose-5-phosphate from 6-phosphogluconate. We report that iron and cysteine interact and have additive effects on the reaction rate so that ribose-5-phosphate forms at high specificity under mild, metabolism typical temperature and environmental conditions. We speculate that accelerating effects of amino acids on rate-limiting nonenzymatic reactions could have facilitated a stepwise enzymatization of nonenzymatic reaction sequences, imprinting their structure on the evolving metabolic network.
dc.languageen
dc.publisherPublic Library of Science (PLoS)
dc.subjectShort Reports
dc.subjectPhysical sciences
dc.subjectBiology and life sciences
dc.subjectComputer and information sciences
dc.titleCysteine and iron accelerate the formation of ribose-5-phosphate, providing insights into the evolutionary origins of the metabolic network structure.
dc.typeArticle
dc.date.updated2022-01-05T10:48:12Z
prism.issueIdentifier12
prism.publicationNamePLoS Biol
prism.volume19
dc.identifier.doi10.17863/CAM.79444
dcterms.dateAccepted2021-11-04
rioxxterms.versionofrecord10.1371/journal.pbio.3001468
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Lane, Nick
dc.contributor.orcidPiedrafita, Gabriel [0000-0001-8701-1084]
dc.contributor.orcidVarma, Sreejith J [0000-0002-1669-2254]
dc.contributor.orcidRalser, Markus [0000-0001-9535-7413]
dc.identifier.eissn1545-7885
pubs.funder-project-idCancer Research UK (FC001134)
pubs.funder-project-idUK Medical Research Council (FC001134)
pubs.funder-project-idWellcome Trust (FC001134)
pubs.funder-project-idWellcome Trust (200829/Z/16/Z)
pubs.funder-project-idBundesministerium für Bildung und Forschung (031L0220A)
pubs.funder-project-idUK Medical Research Council (MR/P011705/1)
pubs.funder-project-idUK Medical Research Council (MC_UP_A090_1006)
pubs.funder-project-idComunidad de Madrid (Talento program fellowship)
cam.issuedOnline2021-12-03


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