{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:03:01Z","timestamp":1781071381436,"version":"3.54.1"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Carlos III Institute of Health of Spain","award":["PI125\/00257"],"award-info":[{"award-number":["PI125\/00257"]}]},{"name":"SEIMC-Fundaci\u00f3n Soria Melguizo 2021 Research Award, the CIBER-Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica en Red CIBERESP","award":["CB06\/02\/0053"],"award-info":[{"award-number":["CB06\/02\/0053"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>The possibility of the emergence of proto-antibiotic and proto-resistance molecules in the prebiotic world, as primary elements involved in \u201cmolecular wars,\u201d is examined in this conceptual review. Throughout the Earth\u2019s early history, prebiotic chemical processes produced molecules that associated both randomly and persistently. Over time, those configurations that achieved greater stability were favored, their longevity effectively serving as a mechanism for prebiotic selection. Available chemical molecules or physical surfaces could stabilize and prolong the duration of certain aggregates, creating competition among them. Hypothetically, some aggregates could yield conformations capable of disrupting the assembly or stability of rival structures, thereby acting as proto-antimolecules and later evolving into proto-antibiotics in a primitive cellular scenario. Concurrently, some other molecular aggregates may deactivate such proto-antimolecules and antibiotics, acting as primitive mechanisms of resistance. Probably, both production and protection mechanisms tended to coalesce in multimolecular assemblies, ensuring the non-self-destruction of producers. Over a prolonged period, the chemical Thioester World, RNA World, and the biological Proto-Cellular World coexisted, and proto-organelles began to be influenced and protected by proto-antibiotics and proto-resistances. Antibiotic production and resistance remained associated, even at the stage of antibiotic polyketides, which progressively emerged in a more oxygenated landscape, with early biosynthetic pathways giving rise to contemporary ones, mainly in Actinomycota. This simultaneous action-and-reaction scenario provided an ecological equilibrium in which antibiotic molecules were not necessarily killer agents but rather regulatory signals within the microbiosphere, ensuring healthy bacterial interactions. The massive anthropogenic antibiotic production altered such an equilibrium, favoring an unbalanced resistance reaction through the massive diffusion of antibiotic resistance genes, now decoupled from antibiotic production and spreading across the microbial world, mostly carried in mobile genetic elements.<\/jats:p>","DOI":"10.3389\/fmicb.2026.1851874","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:40:55Z","timestamp":1781070055000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular war and peace: the concurrent path to antibiosis and antibiotic resistance"],"prefix":"10.3389","volume":"17","author":[{"given":"Fernando","family":"Baquero","sequence":"first","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Instituto Ram\u00f3n y Cajal de Investigaciones Sanitarias (IRYCIS)","place":["Madrid, Spain"]},{"name":"Centro de Investigaci\u00f3n M\u00e9dica en Red \u2013 Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Cant\u00f3n","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Instituto Ram\u00f3n y Cajal de Investigaciones Sanitarias (IRYCIS)","place":["Madrid, Spain"]},{"name":"Centro de Investigaci\u00f3n M\u00e9dica en Red \u2013 Enfermedades Infecciosas (CIBERINFEC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Herencias","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Instituto Ram\u00f3n y Cajal de Investigaciones Sanitarias (IRYCIS)","place":["Madrid, Spain"]},{"name":"Centro de Investigaci\u00f3n M\u00e9dica en Red \u2013 Enfermedades Infecciosas (CIBERINFEC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o A.","family":"Gama","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Instituto Ram\u00f3n y Cajal de Investigaciones Sanitarias (IRYCIS)","place":["Madrid, Spain"]},{"name":"Centro de Investigaci\u00f3n M\u00e9dica en Red \u2013 Enfermedades Infecciosas (CIBERINFEC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa M.","family":"Coque","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Instituto Ram\u00f3n y Cajal de Investigaciones Sanitarias (IRYCIS)","place":["Madrid, Spain"]},{"name":"Centro de Investigaci\u00f3n M\u00e9dica en Red \u2013 Enfermedades Infecciosas (CIBERINFEC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e02993","DOI":"10.1002\/chem.202502993","article-title":"Stimuli-responsive chemical systems that mimic biological dynamics","volume":"32","author":"Aguanell","year":"2026","journal-title":"Chem. Eur. J."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nrmicro2312","article-title":"Call of the wild: antibiotic resistance genes in natural environments","volume":"8","author":"Allen","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref3","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1511\/2003.12.138","article-title":"New antibiotics and new resistance","volume":"91","author":"Am\u00e1bile-Cuevas","year":"2003","journal-title":"Am. Sci."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2970","DOI":"10.1111\/j.1462-2920.2009.01972.x","article-title":"The role of antibiotics and antibiotic resistance in nature","volume":"11","author":"Aminov","year":"2009","journal-title":"Environ. Microbiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1128\/AAC.37.8.1563","article-title":"Genetics and mechanisms of Glycopeptide resistance in enterococci","volume":"37","author":"Arthur","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"10766294261431312","DOI":"10.1177\/10766294261431312","article-title":"Cell wall bioactive molecules as signaling and effector agents in bacterial physiology and virulence","volume":"32","author":"Baquero","year":"2026","journal-title":"Microb. Drug Resist."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"uqae025","DOI":"10.1093\/femsml\/uqae025","article-title":"Did organs precede organisms in the origin of life?","volume":"5","author":"Baquero","year":"2024","journal-title":"Microlife"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.mib.2005.02.016","article-title":"Regulation of secondary metabolism in Streptomyces","volume":"8","author":"Bibb","year":"2005","journal-title":"Curr. Opin. Microbiol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3390\/life8040057","article-title":"Exploring the emergence of RNA nucleosides and nucleotides on the early earth","volume":"8","author":"Biscans","year":"2018","journal-title":"Life"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1093\/nar\/gkac052","article-title":"Origin of life: protoribosome forms peptide bonds and links RNA and protein dominated worlds","volume":"50","author":"Bose","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2631","DOI":"10.1021\/cr960018l","article-title":"The mechanism of ACV Synthetase","volume":"97","author":"Byford","year":"1997","journal-title":"Chem. Rev."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/292136a0","article-title":"Prebiotic atmospheric oxygen levels","volume":"292","author":"Carver","year":"1981","journal-title":"Nature"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"6714","DOI":"10.1111\/febs.16554","article-title":"Crystal structure of a family VIII \u03b2-lactamase fold hydrolase reveals the molecular mechanism for its broad substrate scope","volume":"289","author":"Cea-Rama","year":"2022","journal-title":"FEBS J."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"17560","DOI":"10.1038\/s41598-020-74223-5","article-title":"Prebiotic oligomerization and self-assembly of structurally diverse xenobiological monomers","volume":"10","author":"Chandru","year":"2020","journal-title":"Sci. Rep."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1002\/cbdv.200790055","article-title":"Ribozyme catalysis of metabolism in the RNA world","volume":"4","author":"Chen","year":"2007","journal-title":"Chem. Biodivers."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1734985","DOI":"10.3389\/fmicb.2025.1734985","article-title":"Recent advances in the biosynthetic pathway and structural modification of gentamicin","volume":"16","author":"Chen","year":"2025","journal-title":"Front. Microbiol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1146\/annurev-biophys-030722-125440","article-title":"Ancestral reconstruction and the evolution of protein energy landscapes","volume":"53","author":"Chisholm","year":"2024","journal-title":"Annu. Rev. Biophys."},{"key":"ref9002","article-title":"Aminoglycosides: molecular insights on the recognition of RNA and aminoglycoside mimics","volume":"3","author":"Chittapragada","year":"2009","journal-title":"Perspect. Med. Chem."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"4433","DOI":"10.1128\/AAC.00594-16","article-title":"rRNA binding sites and the molecular mechanism of action of the tetracyclines","volume":"60","author":"Chukwudi","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"R437","DOI":"10.1016\/j.cub.2009.04.001","article-title":"The natural history of antibiotics","volume":"19","author":"Clardy","year":"2009","journal-title":"Curr. Biol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/nchem.2624","article-title":"Prebiotic synthesis of phosphoenol pyruvate by \u03b1-phosphorylation-controlled triose glycolysis","volume":"9","author":"Coggins","year":"2017","journal-title":"Nat. Chem."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e2119235119","DOI":"10.1073\/pnas.2119235119","article-title":"Lipid membranes modulate the activity of RNA through sequence-dependent interactions","volume":"119","author":"Czerniak","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1007\/s10295-006-0112-5","article-title":"Are antibiotics naturally antibiotics?","volume":"33","author":"Davies","year":"2006","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref23","first-page":"24","author":"Davies","year":"2007"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1021\/cb200337h","article-title":"Introducing the parvome: bioactive compounds in the microbial world","volume":"7","author":"Davies","year":"2012","journal-title":"ACS Chem. Biol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1089\/153110702762470482","article-title":"The first cell membranes","volume":"2","author":"Deamer","year":"2002","journal-title":"Astrobiology"},{"key":"ref26","first-page":"3","author":"Demain","year":"2007"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/j.1574-6968.1985.tb01002.x","article-title":"Streptomycin biosynthesis in Streptomyces griseus II. Adjacent genomic location of biosynthetic genes and one of two streptomycin resistance genes","volume":"30","author":"Distler","year":"1985","journal-title":"FEMS Microbiol. Lett."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"13359","DOI":"10.1073\/pnas.1810555115","article-title":"HflXr, a homolog of a ribosome-splitting factor, mediates antibiotic resistance","volume":"115","author":"Duval","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e2","DOI":"10.1371\/journal.pcbi.0010002","article-title":"What makes ribosome-mediated transcriptional attenuation sensitive to amino acid limitation?","volume":"1","author":"Elf","year":"2005","journal-title":"PLoS Comput. Biol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.1021\/bi00814a013","article-title":"Ribosome-catalyzed ester formation","volume":"9","author":"Fahnestock","year":"1970","journal-title":"Biochemistry"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"4067","DOI":"10.1021\/acs.jcim.4c02366","article-title":"Nonequilibrium self-assembly control by the stochastic landscape method","volume":"65","author":"Faran","year":"2025","journal-title":"J. Chem. Inf. Model"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/s42003-022-03477-8","article-title":"The Streptomyces viridochromogenes product template domain represents an evolutionary intermediate between dehydratase and aldol cyclase of type I polyketide synthases","volume":"5","author":"Feng","year":"2022","journal-title":"Commun. Biol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.tig.2025.02.004","article-title":"The origins and evolution of translation factors","volume":"41","author":"Fer","year":"2025","journal-title":"Trends Genet."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1089\/ast.2021.0059","article-title":"Synthesis of phospholipids under plausible prebiotic conditions and analogies with phospholipid biochemistry for origin of life studies","volume":"22","author":"Fiore","year":"2022","journal-title":"Astrobiology"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e2500503122","DOI":"10.1073\/pnas.2500503122","article-title":"Protopeptide backbone affects assembly in aqueous solutions","volume":"122","author":"Fisher","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"16338","DOI":"10.1073\/pnas.1904849116","article-title":"Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions","volume":"116","author":"Frenkel-Pinter","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"3137","DOI":"10.1038\/s41467-020-16891-5","article-title":"Mutually stabilizing interactions between proto-peptides and RNA","volume":"11","author":"Frenkel-Pinter","year":"","journal-title":"Nat. Commun."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"4707","DOI":"10.1021\/acs.chemrev.9b00664","article-title":"Prebiotic peptides: molecular hubs in the origin of life","volume":"120","author":"Frenkel-Pinter","year":"","journal-title":"Chem. Rev."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"gzab013","DOI":"10.1093\/protein\/gzab013","article-title":"Evolution of \u03b2-lactamases and enzyme promiscuity","volume":"34","author":"Fr\u00f6hlich","year":"2021","journal-title":"Protein Eng. Des. Sel."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"6887","DOI":"10.1128\/JB.05764-11","article-title":"AmpH, a bifunctional DD-endopeptidase and DD-carboxypeptidase of Escherichia coli","volume":"193","author":"Gonz\u00e1lez-Leiza","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1017\/s0094837300004310","article-title":"Exaptation -a missing term in the science of form","volume":"8","author":"Gould","year":"1982","journal-title":"Paleobiology"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.1128\/JB.00228-12","article-title":"Characterization of the two-component monooxygenase system AlnT\/AlnH reveals early timing of quinone formation in alnumycin biosynthesis","volume":"194","author":"Grocholski","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"7842","DOI":"10.1038\/s41467-023-43451-4","article-title":"Resurrecting ancestral antibiotics: unveiling the origins of modern lipid II targeting glycopeptides","volume":"14","author":"Hansen","year":"2023","journal-title":"Nat. Commun."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e2221984120","DOI":"10.1073\/pnas.2221984120","article-title":"A mineral-based origin of earth\u2019s initial hydrogen peroxide and molecular oxygen","volume":"120","author":"He","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"6112","DOI":"10.1128\/jb.179.19.6112-6121.1997","article-title":"AmpC and AmpH, are highly related to the class C \u03b2-lactamases, and contribute to the normal morphology of Escherichia coli","volume":"179","author":"Henderson","year":"1997","journal-title":"J. Bacteriol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1039\/D5NP00078E","article-title":"Microbial skeletal editing: hints for arene reconstruction from actinobacteria","volume":"43","author":"Ikonnikova","year":"2026","journal-title":"Nat. Prod. Rep."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/s41559-020-01386-9","article-title":"The evolution of oxygen-utilizing enzymes suggests early biosphere oxygenation","volume":"5","author":"Jab\u0142o\u0144ska","year":"2021","journal-title":"Nat. Ecol. Evol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1126\/science.1161527","article-title":"The Miller volcanic spark discharge experiment","volume":"322","author":"Johnson","year":"2008","journal-title":"Science"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"573","DOI":"10.3390\/antibiotics13070573","article-title":"Phylogenetic analysis of the genes in D-ala-D-lactate synthesizing glycopeptide resistance operons: the different origins of functional and regulatory genes","volume":"13","author":"Kardos","year":"2024","journal-title":"Antibiotics"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/bf02101103","article-title":"Evolutionary origin of aminoglycoside phosphotransferase resistance genes","volume":"30","author":"Kirby","year":"1990","journal-title":"J. Mol. Evol."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.gsf.2017.07.007","article-title":"Origins of building blocks of life: a review","volume":"9","author":"Kitadai","year":"2018","journal-title":"Geosci. Front."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1007\/s00239-007-9006-z","article-title":"Molecular evidence for the ancient origin of the ribosomal protection protein that mediates tetracycline resistance in bacteria","volume":"65","author":"Kobayashi","year":"2007","journal-title":"J. Mol. Evol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/ja.2009.76","article-title":"Biosynthetic genes for aminoglycoside antibiotics","volume":"62","author":"Kudo","year":"2009","journal-title":"J. Antibiot."},{"key":"ref9001","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1039\/D2NP00024E","article-title":"Biosynthesis of cyclitols","volume":"39","author":"Kudo","year":"2022","journal-title":"Nat. Prod. Re. p."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3390\/life9020052","article-title":"Prebiotic sugar formation under nonaqueous conditions and mechanochemical acceleration","volume":"9","author":"Lamour","year":"2019","journal-title":"Life"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/s0092-8674(00)81263-5","article-title":"The origin and early evolution of life: prebiotic chemistry, the pre-RNA world, and time","volume":"85","author":"Lazcano","year":"1996","journal-title":"Cell"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1042\/bio03702004","article-title":"Ribozymes: ancient and modern","volume":"37","author":"Lilley","year":"2015","journal-title":"Biochemist"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"19484","DOI":"10.1073\/pnas.0608949103","article-title":"Antibiotics as intermicrobial signaling agents instead of weapons","volume":"103","author":"Linares","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.cbpa.2009.02.030","article-title":"Progress in aminocyclitol biosynthesis","volume":"13","author":"Mahmud","year":"2009","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.2174\/0929867013371716","article-title":"Glycopeptide derivatives","volume":"8","author":"Malabarba","year":"2001","journal-title":"Curr. Med. Chem."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"e0132689","DOI":"10.1371\/journal.pone.0132689","article-title":"The origin and evolution of Baeyer\u2014Villiger monooxygenases (BVMOs): an ancestral family of Flavin monooxygenases","volume":"10","author":"Mascotti","year":"2015","journal-title":"PLoS One"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"5541","DOI":"10.1016\/j.ejmech.2010.09.035","article-title":"2-Azetidinone--a new profile of various pharmacological activities","volume":"45","author":"Mehta","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.48130\/ebp-0025-0020","article-title":"The hidden mechanistic hand: the mechanical force that drives global biogeochemical cycles","volume":"2","author":"Meng","year":"2025","journal-title":"Environ. Biogeochem. Process."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-4939-3375-4_1","article-title":"Structural biology of nonribosomal peptide synthetases","volume":"1401","author":"Miller","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.tibs.2009.01.005","article-title":"Co-evolution of primordial membranes and membrane proteins","volume":"34","author":"Mulkidjanian","year":"2009","journal-title":"Trends Biochem. Sci."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/s41586-022-04676-3","article-title":"A prebiotically plausible scenario of an RNA\u2013peptide world. 2022","volume":"605","author":"M\u00fcller","year":"2022","journal-title":"Nature"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"12396","DOI":"10.1073\/pnas.1714896114","article-title":"Abiotic production of sugar phosphates and uridine ribonucleoside in aqueous microdroplets","volume":"114","author":"Nam","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1936","DOI":"10.1098\/rstb.2024.0289","article-title":"Can the origin of biosynthetic routes be explained by a Frankenstein\u2019s monster-like spontaneous assembly of prebiotic reactants?","volume":"380","author":"Negr\u00f3n-Mendoza","year":"2025","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"3985","DOI":"10.1038\/s41467-021-23286-7","article-title":"The great oxygenation event as a consequence of ecological dynamics modulated by planetary change","volume":"12","author":"Olejarz","year":"2021","journal-title":"Nat. Commun."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1111\/maps.13794","article-title":"Non-protein amino acids identified in carbon-rich Hayabusa particles","volume":"57","author":"Parker","year":"2022","journal-title":"Meteorit. Planet. Sci."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/proeng\/gzg008","article-title":"Evolutionary engineering of a \u03b2-lactamase activity on a D-ala D-ala transpeptidase fold","volume":"16","author":"Peimbert","year":"2003","journal-title":"Protein Eng."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"154","DOI":"10.3390\/microbiolres16070154","article-title":"Virus-first theory revisited: bridging RNP-world and cellular life","volume":"16","author":"Prosdocimi","year":"2025","journal-title":"Microbiol. Res."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.1126\/science.1118439","article-title":"The effect of oxygen on biochemical networks and the evolution of complex life","volume":"311","author":"Raymond","year":"2006","journal-title":"Science"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3390\/microorganisms7050124","article-title":"Biosynthesis of polyketides in Streptomyces","volume":"7","author":"Risdian","year":"2019","journal-title":"Microorganisms"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"E11943","DOI":"10.1073\/pnas.1812400115","article-title":"Simple yet functional phosphate-loop proteins","volume":"115","author":"Romero Romero","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1021\/cr2004844","article-title":"Prebiotic systems chemistry: new perspectives for the origins of life","volume":"114","author":"Ruiz-Mirazo","year":"2014","journal-title":"Chem. Rev."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"5943","DOI":"10.1002\/anie.201801919","article-title":"Noncanonical RNA nucleosides as molecular fossils of an early earth-generation by prebiotic methylations and carbamoylations","volume":"57","author":"Schneider","year":"2018","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/emboj\/19.1.1","article-title":"Modulation of RNA function by aminoglycoside antibiotics","volume":"19","author":"Schroeder","year":"2000","journal-title":"EMBO J."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3389\/fmicb.2013.00047","article-title":"The multifaceted roles of antibiotics and antibiotic resistance in nature","volume":"4","author":"Sengupta","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"R567","DOI":"10.1016\/j.cub.2009.05.054","article-title":"The continuing puzzle of the great oxidation event","volume":"19","author":"Sessions","year":"2009","journal-title":"Curr. Biol."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.3390\/life11111140","article-title":"Automated exploration of prebiotic chemical reaction space: progress and perspectives","volume":"11","author":"Sharma","year":"2021","journal-title":"Life (Basel)"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"R855","DOI":"10.1016\/j.cub.2015.04.046","article-title":"Photosynthesis and early earth","volume":"25","author":"Shih","year":"2015","journal-title":"Curr. Biol."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1038\/s41586-025-09388-y","article-title":"Thioester-mediated RNA aminoacylation and peptidyl-RNA synthesis in water","volume":"644","author":"Singh","year":"2025","journal-title":"Nature"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1002\/pro.3819","article-title":"Molecular mechanisms of vancomycin resistance","volume":"29","author":"Stogios","year":"2020","journal-title":"Protein Sci."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"2959","DOI":"10.1098\/rstb.2011.0137","article-title":"The RNA origin of transfer RNA aminoacylation and beyond","volume":"366","author":"Suga","year":"2011","journal-title":"Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s10295-016-1850-7","article-title":"\u03b4-(l-\u03b1-aminoadipyl)-l-cysteinyl-d-valine synthetase (ACVS): discovery and perspectives","volume":"44","author":"Tahlan","year":"2017","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.3389\/fmicb.2019.01966","article-title":"Intramolecular interactions dominate the autoregulation of Escherichia coli stringent factor RelA","volume":"10","author":"Turnbull","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.tibs.2018.06.011","article-title":"How macrolide antibiotics work","volume":"43","author":"V\u00e1zquez-Laslop","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"eESP-0027-2020","DOI":"10.1128\/ecosalplus.ESP-0027-2020","article-title":"Ancient antibiotics, ancient resistance","volume":"9","author":"Waglechner","year":"2021","journal-title":"EcoSal Plus"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.1038\/s41564-019-0531-5","article-title":"Phylogenetic reconciliation reveals the natural history of glycopeptide antibiotic biosynthesis and resistance","volume":"4","author":"Waglechner","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12915-017-0423-1","article-title":"Antibiotic resistance: it\u2019s bad, but why isn\u2019t it worse?","volume":"15","author":"Waglechner","year":"2017","journal-title":"BMC Biol."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"e70001","DOI":"10.1002\/wrna.70001","article-title":"Hypothesis for molecular evolution in the pre-cellular stage of the origin of life","volume":"16","author":"Wang","year":"2025","journal-title":"WIREs RNA"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"9259","DOI":"10.1073\/pnas.1401734111","article-title":"Atlas of nonribosomal peptide and polyketide biosynthetic pathways reveals common occurrence of nonmodular enzymes","volume":"111","author":"Wang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/nchem.2427","article-title":"Dissociative electron attachment to CO2 produces molecular oxygen","volume":"8","author":"Wang","year":"2016","journal-title":"Nat. Chem."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"690744","DOI":"10.3389\/fmicb.2021.690744","article-title":"Translational attenuation mechanism of ermB induction by erythromycin is dependent on two leader peptides","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S0076-6879(09)04619-9","article-title":"Enzymology of aminoglycoside biosynthesis\u2014deduction from gene clusters","volume":"459","author":"Wehmeier","year":"2009","journal-title":"Methods Enzymol."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/s41557-022-00982-5","article-title":"Prebiotic synthesis and triphosphorylation of 3\u2032-amino-TNA nucleosides","volume":"14","author":"Whitaker","year":"2022","journal-title":"Nat. Chem."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"100003","DOI":"10.59717\/j.xinn-geo.2023.100003","article-title":"Abiotic oxidants promoted cyanobacteria\u2019s evolution and earth\u2019s oxidation","volume":"1","author":"Wu","year":"2023","journal-title":"Innov. Geosci."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/35000624","article-title":"Alternative modular polyketide synthase expression controls macrolactone structure","volume":"403","author":"Xue","year":"2000","journal-title":"Nature"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"1368809","DOI":"10.3389\/fmicb.2024.1368809","article-title":"The roles of SARP family regulators involved in secondary metabolism in Streptomyces","volume":"15","author":"Yan","year":"2024","journal-title":"Front. Microbiol."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"2522","DOI":"10.1021\/jacsau.3c00299","article-title":"Carbonyl migration in uronates affords a potential prebiotic pathway for pentose production","volume":"3","author":"Yi","year":"2023","journal-title":"JACS Au"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"F1000 Faculty Rev-723","DOI":"10.12688\/f1000research.11104.1","article-title":"Parallel pathways in the biosynthesis of aminoglycoside antibiotics","volume":"6","author":"Yu","year":"2017","journal-title":"F1000 Res."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.3389\/fmicb.2020.01173","article-title":"Glycopeptide antibiotic resistance genes: distribution and function in the producer actinomycetes","volume":"11","author":"Yushchuk","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"102507","DOI":"10.1016\/j.cbpa.2024.102507","article-title":"Recent progresses in the cyclization and oxidation of polyketide biosynthesis","volume":"81","author":"Zhang","year":"2024","journal-title":"Curr. Opin. Chem. Biol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1851874\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:41:03Z","timestamp":1781070063000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1851874\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":105,"alternative-id":["10.3389\/fmicb.2026.1851874"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1851874","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]},"article-number":"1851874"}}