{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:55:41Z","timestamp":1791255341728,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2002,6,1]],"date-time":"2002-06-01T00:00:00Z","timestamp":1022889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2002,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The use of\n            <jats:italic>Lactococcus lactis<\/jats:italic>\n            (the most extensively characterized lactic acid bacterium) as a delivery organism for heterologous proteins is, in some cases, limited by low production levels and poor-quality products due to surface proteolysis. In this study, we combined in one\n            <jats:italic>L. lactis<\/jats:italic>\n            strain use of the nisin-inducible promoter P\n            <jats:italic>\n              <jats:sub>nisA<\/jats:sub>\n            <\/jats:italic>\n            and inactivation of the extracellular housekeeping protease HtrA. The ability of the mutant strain, designated\n            <jats:italic>htrA<\/jats:italic>\n            -NZ9000, to produce high levels of stable proteins was confirmed by using the staphylococcal nuclease (Nuc) and the following four heterologous proteins fused or not fused to Nuc that were initially unstable in wild-type\n            <jats:italic>L. lactis<\/jats:italic>\n            strains: (i)\n            <jats:italic>Staphylococcus hyicus<\/jats:italic>\n            lipase, (ii) the bovine rotavirus antigen nonstructural protein 4, (iii) human papillomavirus antigen E7, and (iv)\n            <jats:italic>Brucella abortus<\/jats:italic>\n            antigen L7\/L12. In all cases, protein degradation was significantly lower in strain\n            <jats:italic>htrA<\/jats:italic>\n            -NZ9000, demonstrating the usefulness of this strain for stable heterologous protein production.\n          <\/jats:p>","DOI":"10.1128\/aem.68.6.3141-3146.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:09:29Z","timestamp":1027764569000},"page":"3141-3146","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":91,"title":["Controlled Production of Stable Heterologous Proteins in\n            <i>Lactococcus lactis<\/i>"],"prefix":"10.1128","volume":"68","author":[{"given":"A.","family":"Miyoshi","sequence":"first","affiliation":[{"name":"Unite\u0301 de Recherches Laitie\u0300res et de Ge\u0301ne\u0301tique Applique\u0301e, INRA, Domaine de Vilvert, 78352 Jouy en Josas cedex, France"},{"name":"Institute of Biological Sciences, Federal University of Minas Gerais (UFMG-ICB), Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Poquet","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Recherches Laitie\u0300res et de Ge\u0301ne\u0301tique Applique\u0301e, INRA, Domaine de Vilvert, 78352 Jouy en Josas cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Federal University of Minas Gerais (UFMG-ICB), Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Commissaire","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Recherches Laitie\u0300res et de Ge\u0301ne\u0301tique Applique\u0301e, INRA, Domaine de Vilvert, 78352 Jouy en Josas cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Bermudez-Humaran","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Recherches Laitie\u0300res et de Ge\u0301ne\u0301tique Applique\u0301e, INRA, Domaine de Vilvert, 78352 Jouy en Josas cedex, France"},{"name":"Laboratorio de Inmunologi\u0301a y Virologi\u0301a, Facultad de Ciencias Biolo\u0301gicas, Universidad Auto\u0301noma de Nuevo Leo\u0301n, San Nicolas de los Garza, Nuevo Leo\u0301n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Domakova","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Recherches Laitie\u0300res et de Ge\u0301ne\u0301tique Applique\u0301e, INRA, Domaine de Vilvert, 78352 Jouy en Josas cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Le Loir","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Recherches Laitie\u0300res et de Ge\u0301ne\u0301tique Applique\u0301e, INRA, Domaine de Vilvert, 78352 Jouy en Josas cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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