{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:00:01Z","timestamp":1785398401644,"version":"3.56.0"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2105400"],"award-info":[{"award-number":["2022YFC2105400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200054"],"award-info":[{"award-number":["32200054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Echinocandin B (ECB), a fungal non\u2010ribosomal lipopeptide, serves as the exclusive natural precursor of the front\u2010line antifungal anidulafungin. Despite its clinical importance, ECB production remains suboptimal due to incomplete understanding of its biosynthesis mechanism. The global regulator LaeA has been implicated in secondary metabolite production, yet its specific role in ECB biosynthesis remains unexplored. To address this, we successfully constructed\n                    <jats:italic>laeA<\/jats:italic>\n                    deletion and overexpression strains, and demonstrated that LaeA functionally couples morphological development with ECB productivity. Transcriptomic analysis revealed LaeA directly activated the sterigmatocystin cluster via pathway\u2010specific regulator AflR, but indirectly influenced ECB through iron\u2010heme cofactor synchronization rather than direct gene cluster activation. LaeA overexpression upregulated siderophore iron transporters and heme biosynthetic genes, with supplementation of Fe\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    or 5\u2010ALA further boosting titers to 2487 \u00b1 123 and 2697 \u00b1 16\u00a0mg\/L, respectively. To overcome P450s catalytic constraints, we screened out a novel cytochrome P450 reductase CPR2 as the optimal redox partner. Co\u2010expression of CPR2 with bacterial hemoglobin VHb achieved synergistic enhancement, improving the ECB titer to 3170 \u00b1 41\u00a0mg\/L. This study provided a practical strategy for improving ECB production and offering insights into the versatile regulatory modes of global secondary metabolite regulators.\n                  <\/jats:p>","DOI":"10.1002\/biot.70275","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T11:17:03Z","timestamp":1782731823000},"source":"Crossref","is-referenced-by-count":0,"title":["LaeA Orchestrates Iron\u2010Heme Supply and P450 Catalytic Efficiency for Enhanced Echinocandin B Biosynthesis in\n                    <i>Aspergillus nidulans<\/i>"],"prefix":"10.1002","volume":"21","author":[{"given":"Xiaozhang","family":"Yang","sequence":"first","affiliation":[{"name":"National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals Zhejiang University of Technology  Hangzhou P. R. China"},{"name":"Zhejiang Tiantai Pharmaceutical Co., Ltd  Taizhou Zhejiang P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals Zhejiang University of Technology  Hangzhou P. R. China"},{"name":"Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology  Hangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Shen","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals Zhejiang University of Technology  Hangzhou P. R. China"},{"name":"Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology  Hangzhou P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhou","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals Zhejiang University of Technology  Hangzhou P. R. China"},{"name":"Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology  Hangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-6032","authenticated-orcid":false,"given":"Junping","family":"Zhou","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals Zhejiang University of Technology  Hangzhou P. R. China"},{"name":"Zhejiang Key Laboratory of Green Biomanufacturing of Functional Sugar Alcohols Zhejiang University of Technology  Hangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Pang","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals Zhejiang University of Technology  Hangzhou P. R. China"},{"name":"Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology  Hangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianggang","family":"Huang","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals Zhejiang University of Technology  Hangzhou P. R. China"},{"name":"Zhejiang Key Laboratory of Green Biomanufacturing of Functional Sugar Alcohols Zhejiang University of Technology  Hangzhou P. R. 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