{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:34:42Z","timestamp":1792481682444,"version":"4.5.0"},"reference-count":118,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Riboflavin (vitamin B2) is an essential precursor of flavin cofactors involved in redox metabolism, and its industrial production increasingly relies on microbial fermentation.\n                    <jats:italic>Debaryomyces hansenii<\/jats:italic>\n                    is a halotolerant flavinogenic yeast previously exploited for riboflavin biosynthesis; however, its biotechnological application has been limited by genetic instability and incomplete understanding of its regulatory networks. Here, we reveal a novel connection between the High Osmolarity Glycerol (HOG) pathway and riboflavin metabolism in\n                    <jats:italic>D. hansenii<\/jats:italic>\n                    . Using a stable\n                    <jats:italic>Dhhog1<\/jats:italic>\n                    \u0394 mutant, we demonstrate that loss of\n                    <jats:italic>Dh<\/jats:italic>\n                    Hog1 leads to earlier secretion of riboflavin under acidic and saline conditions, visible as a yellow fluorescent pigment in the culture medium. This early riboflavin accumulation was accompanied by altered assimilation of phosphorus, sulfur, and magnesium but not iron, suggesting that regulation extends beyond classical iron limitation. Gene expression analyses showed up-regulation of\n                    <jats:italic>RIB1<\/jats:italic>\n                    ,\n                    <jats:italic>RIB4<\/jats:italic>\n                    , and\n                    <jats:italic>RIB6<\/jats:italic>\n                    , together with derepression of\n                    <jats:italic>SEF1<\/jats:italic>\n                    , indicating that\n                    <jats:italic>Dh<\/jats:italic>\n                    Hog1 modulates the timing of riboflavin production. These findings uncover a previously unrecognized role of the HOG pathway in coordinating stress responses with secondary metabolism and highlight\n                    <jats:italic>D. hansenii<\/jats:italic>\n                    as a promising platform for metabolic engineering of riboflavin production.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1746023","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T06:42:04Z","timestamp":1771569724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hog1 MAP kinase modulates early riboflavin accumulation under low-pH and saline conditions in Debaryomyces hansenii"],"prefix":"10.3389","volume":"17","author":[{"given":"Diana","family":"Villarreal-Huerta","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias","place":["Mexico City, Mexico"]},{"name":"Posgrado en Ciencias Biol\u00f3gicas","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjam\u00edn","family":"Mendoza-T\u00e9llez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias","place":["Mexico City, Mexico"]},{"name":"Posgrado en Ciencias Bioqu\u00edmicas","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1ngel","family":"Rosas-Paz","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias","place":["Mexico City, Mexico"]},{"name":"Posgrado en Ciencias Biol\u00f3gicas","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma Silvia","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Molecular, Instituto de Fisiolog\u00eda Celular, Universidad Nacional Aut\u00f3noma de M\u00e9xico","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raziel Arturo","family":"Jim\u00e9nez-Nava","sequence":"additional","affiliation":[{"name":"Departamento de Ingenier\u00eda Bioqu\u00edmica, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Unidad Profesional Adolfo L\u00f3pez Mateos","place":["Mexico City, Mexico"]},{"name":"Departamento de Microbiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliseo","family":"Cristiani-Urbina","sequence":"additional","affiliation":[{"name":"Departamento de Ingenier\u00eda Bioqu\u00edmica, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Unidad Profesional Adolfo L\u00f3pez Mateos","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Segal-Kischinevzky","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1128\/MMBR.00030-10","article-title":"Genetic control of biosynthesis and transport of riboflavin and flavin nucleotides and construction of robust biotechnological producers.","volume":"75","author":"Abbas","year":"2011","journal-title":"Microbiol. 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