{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:28:04Z","timestamp":1792020484646,"version":"4.4.0"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"National Key Research and Development Program of MOST of China","doi-asserted-by":"publisher","award":["2024YFA0918103"],"award-info":[{"award-number":["2024YFA0918103"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2024YFA0918103"],"award-info":[{"award-number":["2024YFA0918103"]}],"id":[{"id":"https:\/\/ror.org\/027s68j25","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Producing single-cell protein (SCP) from syngas-derived ethanol and acetate offers a sustainable solution to global protein shortages, yet microbial utilization mechanisms for these mixtures remain underexplored. This study establishes a systematic bioconversion strategy using Cyberlindnera jadinii TU389. To mitigate acetaldehyde accumulation during ethanol metabolism, we engineered the strain TU546 to overexpress acylating acetaldehyde dehydrogenase (ADA6). TU546 achieved a maximum biomass of 46.7 g\/L and a protein yield of 21.69 g\/L, representing enhancements of 28.16% and 23.02% over the wild-type, respectively. Transcriptomic analysis revealed extensive metabolic reprogramming. In the C2 assimilation pathway, upregulated aldehyde dehydrogenase and acetyl-CoA Synthetase 1 accelerated acetate conversion to acetyl-CoA, while downregulated pyruvate decarboxylase and alcohol dehydrogenase minimized carbon flux loss. The upregulation of tricarboxylic acid cycle enzymes, the glyoxylate shunt, and acyl-coA oxidase improved carbon skeleton retention. Moreover, the upregulation of transaminases and N-acetylglutamate synthase, synergized with intensified cell proliferation signaling, redirected amino acid metabolism toward a synthesis-enhanced and degradation-controlled paradigm. This synergistic regulatory network drives the high-efficiency bioconversion of ethanol and acetate into SCP, establishing a molecular mechanistic foundation for the valorization of syngas-derived C2 substrates in biological macromolecule production.<\/jats:p>","DOI":"10.3390\/foods15091464","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:38:14Z","timestamp":1776854294000},"page":"1464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enhanced Biomass and Protein Synthesis in Engineered Cyberlindnera jadinii Growing on Ethanol\/Acetate: Metabolic Engineering and Transcriptomic Mechanism"],"prefix":"10.3390","volume":"15","author":[{"given":"Yixin","family":"Cao","sequence":"first","affiliation":[{"name":"College of Food Science & Technology, Hebei Normal University of Science & Technology, Qinhuangdao 066004, China"},{"name":"Tianjin Key Laboratory for Industrial Biological System and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longxue","family":"Ma","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Industrial Biological System and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxiang","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Industrial Biological System and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Industrial Biological System and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Duan","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Industrial Biological System and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqin","family":"Bai","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Industrial Biological System and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liucheng","family":"Long","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Industrial Biological System and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengbao","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Food Science & Technology, Hebei Normal University of Science & Technology, Qinhuangdao 066004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limei","family":"Chen","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Industrial Biological System and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demao","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Industrial Biological System and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/nyas.12500","article-title":"Production and supply of high-quality food protein for human consumption: Sustainability, challenges, and innovations","volume":"1321","author":"Wu","year":"2014","journal-title":"Ann. 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