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On this basis, a series of\n                      <jats:italic>P. pastoris<\/jats:italic>\n                      strains with knockout or overexpression of transcription factors were constructed and the deletion of transcription factor binding sites on pGAP was confirmed. The results showed that Loc1p and Msn2p can inhibit the activity of pGAP, while Gsm1p and Hot1p can enhance the activity of pGAP; Loc1p, Gsm1p and Hot1p can bind directly to pGAP, while Msn2p must be treated to expose the C-terminal domain to bind to pGAP. Moreover, manipulating a single transcription factor led to a 0.96-fold to 2.43-fold increase in xylanase expression. In another model protein, aflatoxin oxidase, knocking out\n                      <jats:italic>Loc1<\/jats:italic>\n                      based on\n                      <jats:italic>AFO-\u2206Msn2<\/jats:italic>\n                      strain resulted in a 0.63-fold to 1.4-fold increase in expression. It can be demonstrated that the combined use of transcription factors can further improve the expression of exogenous proteins in\n                      <jats:italic>P. pastoris<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings will contribute to the construction of pGAP-based\n                      <jats:italic>P. pastoris<\/jats:italic>\n                      systems towards high expression of heterologous proteins, hence improving the application potential of yeast.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12934-024-02435-9","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T21:02:25Z","timestamp":1721768545000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Novel transcriptional regulation of the GAP promoter in Pichia pastoris towards high expression of heterologous proteins"],"prefix":"10.1186","volume":"23","author":[{"given":"Xiangna","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqiu","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianna","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,24]]},"reference":[{"key":"2435_CR1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/j.1574-6976.2000.tb00532.x","volume":"24","author":"JL Cereghino","year":"2000","unstructured":"Cereghino JL, Cregg JM. 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