{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:03:46Z","timestamp":1790348626295,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["402439\/2013\u20109"],"award-info":[{"award-number":["402439\/2013\u20109"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["314724\/2021\u20104"],"award-info":[{"award-number":["314724\/2021\u20104"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Over the past 50 years, the\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    S2 cells have been valued for their ability to synthesize therapeutic molecules at high yield. To further increase protein expression, it is imperative to improve cellular performance, which is intrinsically linked to cell metabolism. Nevertheless, information on S2 metabolism, including pathways, components, and cellular compartments, remains limited, hindering advances in S2 cellular performance. Herein, using a genetically modified S2 cell line expressing the recombinant rabies virus glycoprotein (RVGP), we investigated the stress caused by RVGP production on S2 cells. Batch cultures using wild\u2010 and rec\u2010types were performed, and 27 compounds were quantified over 192 h. The extracellular metabolome affected the rec\u2010S2 growth kinetics after RVGP expression was activated. Although RVGP was produced in high amounts, we identified a substrate limitation for rec\u2010S2 cell growth (glutamine), changes in amino acid routes due to RVGP biosynthesis (leucine, serine, glycine, and valine), and metabolites that might be affecting rec\u2010S2 cell growth (acetate, pyruvate, citrate, and malate). Organic acid analysis indicated that malate and acetate production are correlated with RVGP production. This work revealed metabolic correlations in S2 cells that may have direct implications for media optimization and yield maximization, thereby improving S2 performance for scale\u2010up.\n                  <\/jats:p>","DOI":"10.1002\/biot.70307","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:53:59Z","timestamp":1789106039000},"source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Footprint of\n                    <i>Drosophila<\/i>\n                    S2 Cells: Findings During the Production of a Recombinant Rabies Virus Glycoprotein"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7100-3394","authenticated-orcid":false,"given":"Monize Caiado","family":"Decarli","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering Federal University of S\u00e3o Carlos  S\u00e3o Carlos S\u00e3o Paulo Brazil"},{"name":"Department of Engineering of Materials and of Bioprocesses School of Chemical Engineering University of Campinas  S\u00e3o Paulo Brazil"},{"name":"Department of Biomaterials &amp;\u00a0Biomedical Technology University Medical Center Groningen\/University of Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8491-8833","authenticated-orcid":false,"given":"Diogo Peres","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Federal University of S\u00e3o Carlos  S\u00e3o Carlos S\u00e3o Paulo Brazil"},{"name":"National Institute for Bioprocessing Research and Training (NIBRT)  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Matilde","family":"Correia","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Federal University of S\u00e3o Carlos  S\u00e3o Carlos S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amadeus Gomes","family":"de Azevedo","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Federal University of S\u00e3o Carlos  S\u00e3o Carlos S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio Alberto Torres","family":"Suazo","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Federal University of S\u00e3o Carlos  S\u00e3o Carlos S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5813-332X","authenticated-orcid":false,"given":"\u00c2ngela Maria","family":"Moraes","sequence":"additional","affiliation":[{"name":"Department of Engineering of Materials and of Bioprocesses School of Chemical Engineering University of Campinas  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato Mancini","family":"Astray","sequence":"additional","affiliation":[{"name":"Multipurpose Laboratory Butantan 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