{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:49:09Z","timestamp":1791470949965,"version":"4.3.4"},"reference-count":65,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T00:00:00Z","timestamp":1617840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"publisher","award":["OTKA 42752"],"award-info":[{"award-number":["OTKA 42752"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>At the focus of abiotic chemical reactions is the synthesis of ribose. No satisfactory explanation was provided as to the missing link between the prebiotic synthesis of ribose and prebiotic RNA (preRNA). Hydrogen cyanide (HCN) is assumed to have been the principal precursor in the prebiotic formation of aldopentoses in the formose reaction and in the synthesis of ribose. Ribose as the best fitting aldopentose became the exclusive sugar component of RNA. The elevated yield of ribose synthesis at higher temperatures and its protection from decomposition could have driven the polymerization of the ribose-phosphate backbone and the coupling of nucleobases to the backbone. RNA could have come into being without the involvement of nucleotide precursors. The first nucleoside monophosphate is likely to have appeared upon the hydrolysis of preRNA contributed by the presence of reactive 2\u2032-OH moieties in the preRNA chain. As a result of phosphorylation, nucleoside monophosphates became nucleoside triphosphates, substrates for the selective synthesis of genRNA.<\/jats:p>","DOI":"10.3390\/ijms22083857","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T11:58:45Z","timestamp":1617883125000},"page":"3857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Prebiotic Pathway from Ribose to RNA Formation"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6304-7653","authenticated-orcid":false,"given":"Gaspar","family":"Banfalvi","sequence":"first","affiliation":[{"name":"Department of Molecular Biotechnology and Microbiology, University of Debrecen, 1 Egyetem Square, 4010 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,8]]},"reference":[{"key":"ref_1","first-page":"60","article-title":"Evidence for early life in Earth\u2019s oldest hydrothermal vent precipitates","volume":"543","author":"Dodd","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1089\/ast.2015.1406","article-title":"The Origin of Life in Alkaline Hydrothermal Vents","volume":"16","author":"Sojo","year":"2016","journal-title":"Astrobioogy"},{"key":"ref_3","first-page":"248","article-title":"Chemical evolution and the origin of life","volume":"44","author":"Calvin","year":"1956","journal-title":"Am. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.envpol.2007.02.006","article-title":"Dynamics of trace metals in organisms and ecosystems: Prediction of metal bioconcentration in different organisms and estimation of exposure risks","volume":"150","author":"Markert","year":"2007","journal-title":"Environ. Pollut."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Markert, B., Fr\u00e4nzle, S., and W\u00fcnschmann, S. (2015). Chemical Evolution: The Biological System of Elements, Springer International.","DOI":"10.1007\/978-3-319-14355-2"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1039\/p19820001975","article-title":"Formose reactions. Part 3. Selective formose reaction catalyzed by organic bases","volume":"1","author":"Matsumoto","year":"1982","journal-title":"J. Chem. Soc. Perkin Trans."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9457","DOI":"10.1021\/ja201769f","article-title":"Synthesis of carbohydrates in mineral-guided prebiotic cycles","volume":"133","author":"Kim","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11324","DOI":"10.1021\/acs.jpcb.0c07070","article-title":"Autocatalysis in Formose Reaction and Formation of RNA Nucleosides","volume":"124","author":"Jeilani","year":"2020","journal-title":"J. Phys. Chem. B"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Omran, A., Menor-Salvan, C., Springsteen, G., and Pasek, M. (2020). The Messy Alkaline Formose Reaction and Its Link to Metabolism. Life, 10.","DOI":"10.3390\/life10080125"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1089\/ast.2020.2216","article-title":"Cometary Glycolaldehyde as a Source of pre-RNA Molecules","volume":"20","author":"Zellner","year":"2020","journal-title":"Astrobiology"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Omran, A. (2020). Plausibility of the Formose Reaction in Alkaline Hydrothermal Vent Environments. Orig. Life Evol. Biosph., 1\u201313.","DOI":"10.1007\/s11084-020-09599-5"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"24440","DOI":"10.1073\/pnas.1907169116","article-title":"Extraterrestrial ribose and other sugars in primitive meteorites","volume":"116","author":"Furukawa","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s11084-013-9350-5","article-title":"Selective Stabilization of Ribose by Borate","volume":"43","author":"Furukawa","year":"2013","journal-title":"Orig. Life Evol. Biosph."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s11084-015-9472-z","article-title":"Effects of Silicate, Phosphate, and Calcium on the Stability of Aldopentoses","volume":"46","author":"Nitta","year":"2015","journal-title":"Orig. Life Evol. Biosphere"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1126\/science.1246704","article-title":"Many Paths to the Origin of Life","volume":"343","author":"Gollihar","year":"2014","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1089\/ast.2010.0508","article-title":"On the Stabilization of Ribose by Silicate Minerals","volume":"11","author":"Horton","year":"2011","journal-title":"Astrobiology"},{"key":"ref_17","first-page":"219","article-title":"A formal test of the theory of universal common ancestry","volume":"465","author":"Theobald","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1089\/dna.2019.4943","article-title":"Ribose Selected as Precursor to Life","volume":"39","author":"Banfalvi","year":"2020","journal-title":"DNA Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/S0040-4020(01)99315-9","article-title":"HCN and chemical evolution: The possible role of cyano compounds in prebiotic synthesis","volume":"40","author":"Ferris","year":"1984","journal-title":"Tetrahedron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/anie.201506585","article-title":"The Origin of Life-Out of the Blue","volume":"55","author":"Sutherland","year":"2016","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-06489-1","article-title":"High Energy Radical Chemistry Formation of HCN-rich Atmospheres on early Earth","volume":"7","author":"Ferus","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5566","DOI":"10.1039\/C8CC01499J","article-title":"Photochemical reductive homologation of hydrogen cyanide using sulfite and ferrocyanide","volume":"54","author":"Xu","year":"2018","journal-title":"Chem. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1089\/ast.2017.1770","article-title":"Sulfidic Anion Concentrations on Early Earth for Surficial Origins-of-Life Chemistry","volume":"18","author":"Ranjan","year":"2018","journal-title":"Astrobiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1073\/pnas.1301522110","article-title":"Transketolase reaction under credible prebiotic conditions","volume":"110","author":"Breslow","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","unstructured":"Miller, S.L., and Orgel, L.E. (1973). The Origins of Life on the Earth, Prentice-Hall."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6662","DOI":"10.1029\/JC088iC11p06662","article-title":"Photochemical reactions of carbon monoxide and water in Earth\u2019s primitive atmosphere","volume":"88","author":"Chang","year":"1983","journal-title":"Geophys. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nature02260","article-title":"Dating the rise of the atmospheric oxygen","volume":"427","author":"Bekker","year":"2004","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1111\/pala.12178","article-title":"Cyanobacteria and the Great Oxidation Event: Evidence from genes and fossils","volume":"58","author":"Schirrmeister","year":"2015","journal-title":"Palaeontology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1900035","DOI":"10.1002\/syst.201900035","article-title":"When Did Life Likely Emerge on Earth in an RNA-First Process?","volume":"2","author":"Benner","year":"2020","journal-title":"ChemSystemsChem"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"B\u00e1nfalvi, G. (2011). Heavy Metals, Trace Elements and Their Cellular Effects, Springe.","DOI":"10.1007\/978-94-007-0428-2_1"},{"key":"ref_31","first-page":"145","article-title":"Formation Synth\u00e9tique d\u2019une Substance Sucr\u00e9e","volume":"53","author":"Boutlerow","year":"1861","journal-title":"CR Acad. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"769","DOI":"10.2174\/138527212799957968","article-title":"The formose reaction: A tool to produce synthetic carbohydrates within a regenerative life support system","volume":"16","author":"Zafar","year":"2012","journal-title":"Curr. Org. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1002\/cssc.201400040","article-title":"Catalytic Formation of Monosaccharides: From the Formose Reaction towards Selective Synthesis","volume":"7","author":"Delidovich","year":"2014","journal-title":"ChemSusChem"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S0040-4039(01)99487-0","article-title":"On the mechanism of the formose reaction","volume":"1","author":"Breslow","year":"1959","journal-title":"Tetrahedron Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1021\/ja00191a008","article-title":"Auto-catalysis and apparent bistability in the formose reaction","volume":"111","author":"Huskey","year":"1989","journal-title":"Am. Chem. Soc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1002\/hlca.19900730526","article-title":"Chemie von a-Aminonitrilen. Aldomerisierung von Glycolaldehyd-phosphat zu racemischen Hexose-2,4,6-triphosphaten und (in Gegenwart von Formaldehyd) racemischen Pentose-2,4-diphosphaten: Rac-Allose-2,4,6-triphosphat und rac-Ribose-2,4-diphosphat sind die R","volume":"73","author":"Pitsch","year":"1990","journal-title":"Helv. Chim. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12821","DOI":"10.1016\/j.tet.2007.10.012","article-title":"The search for the chemistry of life\u2019s origin","volume":"63","author":"Eschenmoser","year":"2007","journal-title":"Tetrahedron"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1039\/c1nj20191c","article-title":"Hydrothermal formose reaction","volume":"35","author":"Kopetzky","year":"2011","journal-title":"New J. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lamour, S., Pallmann, S., Haas, M., and Trapp, O. (2019). Prebiotic Sugar Formation Under Nonaqueous Conditions and Mechanochemical Acceleration. Life, 9.","DOI":"10.3390\/life9020052"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/nchem.296","article-title":"Sugar synthesis in a protocellular model leads to a cell signalling response in bacteria","volume":"1","author":"Gardner","year":"2009","journal-title":"Nat. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1089\/dna.2006.25.189","article-title":"Why ribose was selected as the sugar component of nucleic acids","volume":"25","author":"Banfalvi","year":"2006","journal-title":"DNA Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1016\/j.tet.2008.11.047","article-title":"Synthesis and pharmaceutical application of l-ribose","volume":"65","author":"Okano","year":"2009","journal-title":"Tetrahedron"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0003-9861(61)90033-9","article-title":"Synthesis of purines under possible primitive earth conditions. I. Adenine from hydrogen cyanide","volume":"94","author":"Kimball","year":"1961","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/0022-2836(68)90314-8","article-title":"Studies in prebiotic synthesis. 3. synthesis of pyrimidines from cyanoacetylene and cyanate","volume":"33","author":"Ferris","year":"1968","journal-title":"J. Mol. Biol."},{"key":"ref_45","first-page":"19","article-title":"Synthesis, Properties and Dimerization Study of Isocyanic Acid","volume":"57","author":"Fischer","year":"2002","journal-title":"Z. Nat. B"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1111\/j.1742-4658.2006.05155.x","article-title":"Pentose hosphates in nucleoside interconversion and catabolism","volume":"273","author":"Tozzi","year":"2006","journal-title":"FEBS. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.cub.2016.12.001","article-title":"How life can arise from chemistry","volume":"26","author":"Gross","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0008-6215(98)00040-8","article-title":"13C-labeled aldopentoses: Detection and quantitation of cyclic and acyclic forms by heteronuclear 1D and 2D NMR spectroscopy","volume":"307","author":"Drew","year":"1998","journal-title":"Carbohydr. Res."},{"key":"ref_49","first-page":"41","article-title":"The Bakerian Lecture\u2014Chemical evolution","volume":"288","author":"Calvin","year":"1965","journal-title":"Proc. R. Soc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.1021\/jo01263a132","article-title":"Phosphorylation of d-ribose in aqueous solution","volume":"34","author":"Halmann","year":"1969","journal-title":"J. Org. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1039\/C8CC08510B","article-title":"Regioselective 5\u2032-position phosphorylation of ribose and ribonucleosides: Phosphate transfer in the activated pyrophosphate complex in the gas phase","volume":"55","author":"Hu","year":"2018","journal-title":"Chem. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0022-2836(85)90104-4","article-title":"Origin and degradation of the RNA primers at the 5\u2032 termini of nascent DNA chains in Bacillus subtilis","volume":"186","author":"Sarkar","year":"1985","journal-title":"J. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0022-2836(68)90392-6","article-title":"The origin of the genetic code","volume":"38","author":"Crick","year":"1968","journal-title":"J. Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11084-012-9321-2","article-title":"A Model for the Origin of Life through Rearrangements among Prebiotic Phosphodiester Polymers","volume":"43","author":"Yakhnin","year":"2013","journal-title":"Orig. Life Evol. Biosph."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s00239-014-9640-1","article-title":"Purine Biosynthetic Intermediate-Containing Ribose-Phosphate Polymers as Evolutionary Precursors to RNA","volume":"79","author":"Bernhardt","year":"2014","journal-title":"J. Mol. Evol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8158","DOI":"10.1073\/pnas.92.18.8158","article-title":"Rates of decomposition of ribose and other sugars: Implications for chemical evolution","volume":"92","author":"Larralde","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"15834","DOI":"10.1002\/chem.201601418","article-title":"Thermal Behavior of d-Ribose Adsorbed on Silica: Effect of Inorganic Salt Coadsorption and Significance for Prebiotic Chemistry","volume":"22","author":"Akouche","year":"2016","journal-title":"Chem. Eur. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1126\/science.2434996","article-title":"Why nature chose phosphates","volume":"235","author":"Westheimer","year":"1987","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1002\/chem.200802656","article-title":"Synthesis of Pyrimidines and Triazines in Ice: Implications for the Prebiotic Chemistry of Nucleobases","volume":"15","year":"2009","journal-title":"Chem. Eur. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/s41557-020-00564-3","article-title":"Harnessing chemical energy for the activation and joining of prebiotic building blocks","volume":"12","author":"Liu","year":"2020","journal-title":"Nat. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/319618a0","article-title":"The RNA World","volume":"319","author":"Gilbert","year":"1986","journal-title":"Nature"},{"key":"ref_62","first-page":"a003608","article-title":"The Origins of the RNA World","volume":"4","author":"Robertson","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_63","first-page":"293","article-title":"Ribosomes are optimized for autocatalytic production","volume":"547","author":"Reuveni","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.cbpa.2019.05.018","article-title":"Aptamer-based and aptazyme-based riboswitches in mammalian cells","volume":"52","author":"Yokobayashi","year":"2019","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1745-6150-7-1","article-title":"Evolution before genes","volume":"7","author":"Vasas","year":"2012","journal-title":"Biol. Direct"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/3857\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:12:05Z","timestamp":1760364725000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/3857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,8]]},"references-count":65,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22083857"],"URL":"https:\/\/doi.org\/10.3390\/ijms22083857","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,8]]}}}