{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:43:26Z","timestamp":1784616206751,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004955","name":"\u00d6sterreichische Forschungsf\u00f6rderungsgesellschaft","doi-asserted-by":"publisher","award":["822757"],"award-info":[{"award-number":["822757"]}],"id":[{"id":"10.13039\/501100004955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["W\u20101224\u2010B09"],"award-info":[{"award-number":["W\u20101224\u2010B09"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Letters"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>The tobacco variant <jats:italic>Nicotiana\u00a0benthamiana<\/jats:italic> has recently emerged as a versatile host for the manufacturing of protein therapeutics, but the fidelity of many recombinant proteins generated in this system is compromised by inadvertent proteolysis. Previous studies have revealed that the anti\u2010HIV\u20101 antibodies 2F5 and PG9 as well as the protease inhibitor \u03b1<jats:sub>1<\/jats:sub>\u2010antitrypsin (A1AT) are particularly susceptible to <jats:italic>N<\/jats:italic>.\u00a0<jats:italic>benthamiana<\/jats:italic> proteases. Here, we identify two subtilisin\u2010like serine proteases (NbSBT1 and NbSBT2) whose combined action is sufficient to account for all major cleavage events observed upon expression of 2F5, PG9 and A1AT in <jats:italic>N.\u00a0benthamiana<\/jats:italic>. We propose that downregulation of NbSBT1 and NbSBT2 activities could constitute a powerful means to optimize the performance of this promising platform for the production of biopharmaceuticals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Databases<\/jats:title><jats:p>NbSBT sequence data are available in the DDBJ\/EMBL\/GenBank databases under the accession numbers MN534996 to MN535005.<\/jats:p><\/jats:sec>","DOI":"10.1002\/1873-3468.14014","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T05:05:45Z","timestamp":1606885545000},"page":"379-388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Identification of two subtilisin\u2010like serine proteases engaged in the degradation of recombinant proteins in <i>Nicotiana\u00a0benthamiana<\/i>"],"prefix":"10.1002","volume":"595","author":[{"given":"Alejandro A.","family":"Puchol Tarazona","sequence":"first","affiliation":[{"name":"Department of Applied Genetics and Cell Biology University of Natural Resources and Life Sciences Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Maresch","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Natural Resources and Life Sciences Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Grill","sequence":"additional","affiliation":[{"name":"Department of Applied Genetics and Cell Biology University of Natural Resources and Life Sciences Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Bakalarz","sequence":"additional","affiliation":[{"name":"Department of Applied Genetics and Cell Biology University of Natural Resources and Life Sciences Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan A.","family":"Torres 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