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Herein, we report the identification and characterization of the biosynthetic gene cluster of HA from Trichoderma asperellum. Genetic and biochemical analysis revealed an unexpected pathway to biosynthesize HA from farnesyl pyrophosphate via \u03b1-trans-bergamotene. This pathway involves three redox enzymes acting cooperatively to break down the six-membered ring of bergamotene to generate the skeleton of HA.<\/jats:p>","DOI":"10.1021\/acs.orglett.6c03060","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T18:01:41Z","timestamp":1786730501000},"page":"10802-10808","source":"Crossref","is-referenced-by-count":1,"title":["Cooperation\nof Multi-Redox Enzymes To Biosynthesize\nCyclobutane Sesquiterpenoid Harzianoic Acids from\n                    <i>\u03b1-trans<\/i>\n                    -Bergamotene"],"prefix":"10.1021","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6640-4644","authenticated-orcid":true,"given":"Cheng","family":"Shen","sequence":"first","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, China, 200240"]},{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, China, 201203"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Ting","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, China, 200240"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, China, 200240"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7773-3160","authenticated-orcid":true,"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, China, 200240"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-3239","authenticated-orcid":true,"given":"Man-Cheng","family":"Tang","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, China, 200240"]},{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, China, 201203"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"2026090200175969800_cit1","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.tibtech.2023.12.006","article-title":"Expanding\nthe structural diversity of terpenes by synthetic biology approaches","volume":"42","author":"Chen","year":"2024","journal-title":"Trends Biotechnol."},{"key":"2026090200175969800_cit2","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1039\/D0NP00066C","article-title":"Bacterial\nterpenome","volume":"38","author":"Rudolf","year":"2021","journal-title":"Nat. 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