{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:46:21Z","timestamp":1792784781612,"version":"4.5.0"},"reference-count":58,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"name":"Key Research & Development Projects of Henan Province","award":["241111313000"],"award-info":[{"award-number":["241111313000"]}]},{"name":"Project of Technology Innovation Leading Talent in Central Plain","award":["234200510003"],"award-info":[{"award-number":["234200510003"]}]},{"name":"The Science and Technology Research and Development Plan Joint Fund (Industry) of Henan Province","award":["235101610005"],"award-info":[{"award-number":["235101610005"]}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["32071468"],"award-info":[{"award-number":["32071468"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["U23A20270"],"award-info":[{"award-number":["U23A20270"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chinese hamster ovary (CHO) cells are the predominant host for producing complex recombinant therapeutic proteins. N6-methyladenosine (m6A) regulates recombinant protein production in CHO cells by influencing RNA stability and translation; however, the role of the m6A demethylase ALKBH5 remains poorly characterized in this context. Here, ALKBH5 overexpression increased the titers of three recombinant products by up to 2.87-fold, enhanced CHO cell proliferation, and reduced oxidative stress. Co-immunoprecipitation supported an association between ALKBH5 and ITGB5, and structure-guided mutagenesis identified Tyr205 of ITGB5 as functionally important for this association and ITGB5 protein stability. ALKBH5 overexpression did not measurably alter ITGB5 mRNA stability or m6A enrichment, supporting a mechanism that does not involve detectable m6A changes on the ITGB5 transcript, while not excluding m6A-dependent effects on other targets. FAK inhibition attenuated but did not abolish the production advantage, indicating that FAK signaling contributes to, but may not fully account for, the ALKBH5\u2212ITGB5-associated phenotype. Metabolic and redox measurements further linked ALKBH5 overexpression to increased antioxidant capacity and ATP abundance, together with altered nutrient consumption and by-product formation. These findings identify ALKBH5 as a candidate host-cell engineering target for improving recombinant protein production and support further validation under industry-relevant fed-batch conditions.<\/jats:p>","DOI":"10.1021\/acssynbio.6c00520","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:01:51Z","timestamp":1789149711000},"page":"4291-4306","source":"Crossref","is-referenced-by-count":0,"title":["A Non-Conventional Epigenetic Engineering Strategy: The ALKBH5\/ITGB5 Axis Enhances Recombinant Protein Production in CHO Cells through FAK-Mediated Proliferation and Improved Redox Status"],"prefix":"10.1021","volume":"15","author":[{"given":"Zhao-Ming","family":"Cui","sequence":"first","affiliation":[{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Universiti Sains Malaysia , , Bertam, , ,","place":["Kepala Batas, Penang, Malaysia, 13200"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"The Second Affiliated Hospital, Henan Medical University , , ,","place":["Xinxiang, Henan, China, 453002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-Tao","family":"Lu","sequence":"additional","affiliation":[{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Nankai University , , ,","place":["Tianjin, China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Ping","family":"Gao","sequence":"additional","affiliation":[{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Guo","sequence":"additional","affiliation":[{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin-Qi","family":"Gao","sequence":"additional","affiliation":[{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Ye","family":"Xu","sequence":"additional","affiliation":[{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Qing","family":"Ye","sequence":"additional","affiliation":[{"name":"The Fifth Affiliated Hospital of Henan Medical University , , ,","place":["Xinxiang, Henan, China, 453002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siti Nurfatimah","family":"Mohd Shahpudin","sequence":"additional","affiliation":[{"name":"Universiti Sains Malaysia , , Bertam, , ,","place":["Kepala Batas, Penang, Malaysia, 13200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Ying","family":"Feng","sequence":"additional","affiliation":[{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]},{"name":"The Second Affiliated Hospital, Henan Medical University , , ,","place":["Xinxiang, Henan, China, 453002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le-Le","family":"Qiu","sequence":"additional","affiliation":[{"name":"Henan Medical University , , , ,","place":["Xinxiang, Henan, China, 453003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Henan Medical University , , ,","place":["Xinxiang, China, 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