{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:19:04Z","timestamp":1783448344431,"version":"3.55.0"},"reference-count":78,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Yeast"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Methylotrophic yeasts such as\n                    <jats:italic>Pichia pastoris<\/jats:italic>\n                    are widely used for heterologous protein production because they contain strong and tightly regulated promoters. However, the use of methanol as an inducer presents several practical challenges, including toxicity, flammability, high oxygen demand during fermentation, and increased production costs. To overcome these limitations, researchers have been working on redesigning the\n                    <jats:italic>AOX1<\/jats:italic>\n                    regulatory system and developing alternative induction strategies that do not rely on methanol. One promising approach is optogenetics, which uses light to control gene expression in a non\u2010invasive way. These systems rely on light\u2010sensitive proteins such as phytochromes, cryptochromes, LOV\u2010domain proteins, and UVR8, allowing gene activity to be regulated in a precise and reversible manner without adding chemical inducers to the culture medium. This review brings together key advances in yeast optogenetics, with a focus on the EL222 system, highlighting its implementation for light\u2010controlled heterologous protein production in\n                    <jats:italic>P. pastoris<\/jats:italic>\n                    and its broad application in synthetic biology and metabolic engineering in\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    . The growing versatility and scalability of EL222\u2010based circuits highlight their potential to reshape both fundamental research and industrial bioprocessing through safer, more controllable, and energy\u2010efficient gene regulation strategies.\n                  <\/jats:p>","DOI":"10.1002\/yea.70025","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:00:01Z","timestamp":1778673601000},"page":"130-142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["EL222\u2010Based Optogenetic Gene Regulation in Methylotrophic Yeasts: Mechanisms, Applications, and Future Directions"],"prefix":"10.1002","volume":"43","author":[{"given":"Riya","family":"Joon","sequence":"first","affiliation":[{"name":"Xenesis, Absolute Gurugram Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhythm","family":"Phutela","sequence":"additional","affiliation":[{"name":"Xenesis, 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