{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:20:29Z","timestamp":1773030029947,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2027,2,22]],"date-time":"2027-02-22T00:00:00Z","timestamp":1803254400000},"content-version":"am","delay-in-days":386,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["R43AI136108(NIAID)"],"award-info":[{"award-number":["R43AI136108(NIAID)"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["R44DK129133(NIDDK)"],"award-info":[{"award-number":["R44DK129133(NIDDK)"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diabetes mellitus affects over 500 million people globally, with current insulin therapies relying on subcutaneous injections that compromise the liver's natural role in glucose regulation and suffer from poor patient compliance. Oral insulin delivery offers a physiological alternative but faces challenges, including gastrointestinal degradation and poor absorption. Here, we engineered\n                    <jats:italic>Saccharomyces boulardii<\/jats:italic>\n                    , a probiotic yeast with established gastrointestinal survival capabilities, to secrete a long\u2010acting Insulin\u2010Fc fusion protein (Ins\/Fc). Using strong constitutive promoters (TDH3 and TEF1), we achieved stable expression in lead strains FZ030 and FZ032. The secreted Ins\/Fc fusion protein demonstrated functional bioactivity in cultured cells and in diabetic mice. This represents the first successful engineering of\n                    <jats:italic>S. boulardii<\/jats:italic>\n                    to produce a functional insulin and establishes a promising platform for developing oral insulin delivery systems.\n                  <\/jats:p>","DOI":"10.1002\/biot.70197","type":"journal-article","created":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T14:06:28Z","timestamp":1771769188000},"source":"Crossref","is-referenced-by-count":0,"title":["Engineered Probiotic\n                    <i>Saccharomyces boulardii<\/i>\n                    Produces Functional Insulin With Long\u2010Acting Effect in Mice Model"],"prefix":"10.1002","volume":"21","author":[{"given":"Jefferson J.","family":"Feng","sequence":"first","affiliation":[{"name":"Fzata Inc.  Halethorpe Maryland USA"},{"name":"Department of Microbial Pathogenesis University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Nyasae","sequence":"additional","affiliation":[{"name":"Fzata Inc.  Halethorpe Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Lee","sequence":"additional","affiliation":[{"name":"Fzata Inc.  Halethorpe Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenfen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongrong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1141-9750","authenticated-orcid":false,"given":"Hua","family":"Yu","sequence":"additional","affiliation":[{"name":"Fzata Inc.  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Clinical Review. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK608447\/?utm_source=chatgpt.com."},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007049"}],"container-title":["Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.70197","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/biot.70197","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/biot.70197","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.70197","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:45:24Z","timestamp":1773027924000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/biot.70197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/biot.70197"],"URL":"https:\/\/doi.org\/10.1002\/biot.70197","archive":["Portico"],"relation":{},"ISSN":["1860-6768","1860-7314"],"issn-type":[{"value":"1860-6768","type":"print"},{"value":"1860-7314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"article-number":"e70197"}}