{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:08:21Z","timestamp":1789373301282,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100079"],"award-info":[{"award-number":["32100079"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070123"],"award-info":[{"award-number":["32070123"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp;amp; Bioengineering"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Gibberellins (GAs) are ubiquitous phytohormones that regulate plant growth and are widely used in agriculture. Among these, GA\n                    <jats:sub>3<\/jats:sub>\n                    and GA\n                    <jats:sub>4+7<\/jats:sub>\n                    are the only commercially available products, yet GA\n                    <jats:sub>4+7<\/jats:sub>\n                    commands a much higher price than GA\n                    <jats:sub>3<\/jats:sub>\n                    , primarily due to its low titer in the industrial fungus\n                    <jats:italic>Fusarium fujikuroi<\/jats:italic>\n                    . To engineer a high\u2010yielding GA\n                    <jats:sub>4+7<\/jats:sub>\n                    producer, we first deleted\n                    <jats:italic>p450\u20103<\/jats:italic>\n                    to block the conversion of GA\n                    <jats:sub>4<\/jats:sub>\n                    and GA\n                    <jats:sub>7<\/jats:sub>\n                    to GA\n                    <jats:sub>1<\/jats:sub>\n                    and GA\n                    <jats:sub>3<\/jats:sub>\n                    . This led to the accumulation of GA\n                    <jats:sub>4+7<\/jats:sub>\n                    at 0.934\u2009g\/L, a 37\u2010fold increase over the wild\u2010type strain, albeit with over half reduction in total GA accumulation. Using this \u0394\n                    <jats:italic>p450\u20103<\/jats:italic>\n                    mutant as a platform, we combined metabolic engineering (overexpressing rate\u2010limiting enzymes) with process optimization (pH, medium composition and fermentation duration). These combinatorial interventions synergistically boosted GA\n                    <jats:sub>4+7<\/jats:sub>\n                    production. Under optimized conditions, the engineered strain achieved a final titer of 6.08\u2009g\/L (a 6.51\u2010fold increase over the \u0394\n                    <jats:italic>p450\u20103<\/jats:italic>\n                    parent), comprising 2.13\u2009g\/L GA\n                    <jats:sub>4<\/jats:sub>\n                    and 3.96\u2009g\/L GA\n                    <jats:sub>7<\/jats:sub>\n                    , representing 5.30\u2010 and 7.44\u2010fold increases, respectively. Preliminary optimization in a 10\u2009L fermenter yielded 3.51\u2009g\/L of GA\n                    <jats:sub>4+7<\/jats:sub>\n                    . Finally, a solid\u2010state fermentation system was developed on wheat bran, yielding 17.34\u2009g GA\n                    <jats:sub>4+7<\/jats:sub>\n                    per kg and enabling green, in\u2010house, in\u2010situ gibberellin production. In addition to substantially increasing the GA\n                    <jats:sub>4+7<\/jats:sub>\n                    titer and total GA accumulation, this study demonstrated that the GA\n                    <jats:sub>4<\/jats:sub>\n                    \/GA\n                    <jats:sub>7<\/jats:sub>\n                    ratio can be modulated through both molecular and fermentation strategies.\n                  <\/jats:p>","DOI":"10.1002\/bit.70380","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T07:59:48Z","timestamp":1789372788000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combinatorial Metabolic and Process Engineering for Enhanced GA\n                    <sub>4+7<\/sub>\n                    Production and Tunable GA\n                    <sub>4<\/sub>\n                    \/GA\n                    <sub>7<\/sub>\n                    Ratio in\n                    <i>Fusarium fujikuroi<\/i>"],"prefix":"10.1002","author":[{"given":"Jing\u2010Wen","family":"Jia","sequence":"first","affiliation":[{"name":"State Key Laboratory of Green Chemical Synthesis and Conversion Hangzhou China"},{"name":"Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou China"},{"name":"Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology Hangzhou China"},{"name":"The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng\u2010Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Xianju Junye Pharmaceutical Co. Ltd. Taizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Han","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Chemical Synthesis and Conversion Hangzhou China"},{"name":"Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou China"},{"name":"Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology Hangzhou China"},{"name":"The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi\u2010Yun","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Chemical Synthesis and Conversion Hangzhou China"},{"name":"Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou China"},{"name":"Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology Hangzhou China"},{"name":"The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian\u2010Jie","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Chemical Synthesis and Conversion Hangzhou China"},{"name":"Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou China"},{"name":"Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology Hangzhou China"},{"name":"The National and Local Joint Engineering 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