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Here, we evaluated the glycan distribution of CHO\u2010K1 clones producing adalimumab, a biosimilar version of the anti\u2010TNF antibody Humira. To modulate the glycan profile, the cell culture medium was supplemented with manganese and\/or galactose. Both manganese and galactose increased galactosylation, and the effects were synergistic. Notably, the levels of Man5 were higher than in Humira, even when galactosylation was similar. qPCR analysis revealed few differences in glycosylation enzyme concentrations between different productivity clones or when 50\u00a0\u00b5M manganese was added. We modeled the glycosylation pathways using a dynamic mathematical model to elucidate the mechanisms by which high mannose glycans increased and to develop a more predictive approach to culture modulation. Modeling results suggest that the concentration of uridine triphosphate (UTP), a component of activated sugars, is limiting and that increased uridine diphosphate (UDP)\u2010galactose results in decreased UDP\u2010N\u2010acetylglucosamine, limiting complex glycan synthesis.<\/jats:p>","DOI":"10.1002\/biot.70143","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T06:42:36Z","timestamp":1761547356000},"source":"Crossref","is-referenced-by-count":5,"title":["Modulation of Antibody Glycosylation in Chinese Hamster Ovary Cells: Experimental and Computational Analyses Provide Mechanistic Insights"],"prefix":"10.1002","volume":"20","author":[{"given":"Ranya","family":"Pranomphon","sequence":"first","affiliation":[{"name":"Department of Nanoscale Science and Engineering College of Nanotechnology, Science, and Engineering and The RNA Institute University at Albany, State University of New York  Albany New York USA"},{"name":"School of Biotechnology Institute of Agricultural Technology Suranaree University of Technology  Nakhon Ratchasima Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Gialamoidou","sequence":"additional","affiliation":[{"name":"School of Chemical &amp; Bioprocess Engineering University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montarop","family":"Yamabhai","sequence":"additional","affiliation":[{"name":"School of Biotechnology Institute of Agricultural Technology Suranaree University of Technology  Nakhon Ratchasima Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9289-0191","authenticated-orcid":false,"given":"Ioscani","family":"Jim\u00e9nez del Val","sequence":"additional","affiliation":[{"name":"School of Chemical &amp; Bioprocess Engineering University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0908-4197","authenticated-orcid":false,"given":"Susan T.","family":"Sharfstein","sequence":"additional","affiliation":[{"name":"Department of Nanoscale Science and Engineering College of Nanotechnology, Science, and Engineering and The RNA Institute University at Albany, State University of New York  Albany New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kex278"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2018.01.009"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/BS.S16120"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920108786786358"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2009.00190.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2017.11.001"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216\u2010014\u20108108\u2010x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2006.09.026"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2009.10.008"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616\u2010011\u20109388\u2010z"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253\u2010011\u20103758\u20105"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700234"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25318"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5512.2370"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.01.006"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.7b00199"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/bs.S75573"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1936"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo\u2010116\u20106\u20102293"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.21.6632"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067\u2010016\u20103427\u20102"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-62007-2_6"},{"key":"e_1_2_11_24_1","unstructured":"U.S. Food and Drug Administration. 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