Noncanonical terpene cyclases for the biosynthesis of diterpenoids regulating chlamydospore formation in plant-associated Trichoderma
Abstract Terpene cyclases catalyze exquisite and complicated cyclization reactions to generate diverse terpenoid skeletons. Trichoderma fungi are important biocontrol agents, characteristic of producing complex bioactive tetracyclic diterpenoids named harzianes and trichodermanins, but their biosynt...
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-63055-4 |
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| author | Min-Jie Yang De-Sen Li Hua-Qin Deng Wen-Yuan Li Xin-Yu Zheng Jonathan Gershenzon Xue-Mei Niu Yan Liu Sheng-Hong Li |
| author_facet | Min-Jie Yang De-Sen Li Hua-Qin Deng Wen-Yuan Li Xin-Yu Zheng Jonathan Gershenzon Xue-Mei Niu Yan Liu Sheng-Hong Li |
| author_sort | Min-Jie Yang |
| collection | DOAJ |
| description | Abstract Terpene cyclases catalyze exquisite and complicated cyclization reactions to generate diverse terpenoid skeletons. Trichoderma fungi are important biocontrol agents, characteristic of producing complex bioactive tetracyclic diterpenoids named harzianes and trichodermanins, but their biosynthesis and biological functions have long been enigmatic. Here we identify TriDTCs, an unprecedented family of terpene cyclases in Trichoderma, responsible for cyclizing geranylgeranyl diphosphate (GGPP) into major diterpenes harzianol I and wickerol A, via heterologous expressions, gene deletion, and in vitro assays. TriDTCs represent a brand new class of terpene cyclases, lacking known motifs and diverging from all known enzymes. Mechanistically, TriDTCs likely employ a unique DxxDxxxD aspartate triad for cyclization initiation, a critical valine residue modulating product specificity, and “gatekeeper” residues for activity. Phylogenetic analysis shows TriDTCs have a narrow distribution in three fungal genera and are highly functionally specific within Trichoderma, suggesting a genus-specific acquisition and independent evolution. Functional studies implicated TriDTCs in fungal survival strategies by regulating formation of resistant propagules (chlamydospore in Trichoderma, sclerotia in Aspergillus oryzae). These findings expand the knowledge of terpene cyclase diversity and biological significance, herald a strategy to enhance Trichoderma’s biocontrol efficacy, and open avenues for pharmacological investigation of these diterpenoids. |
| format | Article |
| id | doaj-art-e6a3f90ddc744969ae15bc3cac0ba182 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-e6a3f90ddc744969ae15bc3cac0ba1822025-08-24T11:38:35ZengNature PortfolioNature Communications2041-17232025-08-0116111210.1038/s41467-025-63055-4Noncanonical terpene cyclases for the biosynthesis of diterpenoids regulating chlamydospore formation in plant-associated TrichodermaMin-Jie Yang0De-Sen Li1Hua-Qin Deng2Wen-Yuan Li3Xin-Yu Zheng4Jonathan Gershenzon5Xue-Mei Niu6Yan Liu7Sheng-Hong Li8State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesDepartment of Biochemistry, Max Planck Institute for Chemical EcologySchool of Life Sciences, State Key Laboratory for Conservation and Utilization of Bio-Resources & Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan UniversityState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesAbstract Terpene cyclases catalyze exquisite and complicated cyclization reactions to generate diverse terpenoid skeletons. Trichoderma fungi are important biocontrol agents, characteristic of producing complex bioactive tetracyclic diterpenoids named harzianes and trichodermanins, but their biosynthesis and biological functions have long been enigmatic. Here we identify TriDTCs, an unprecedented family of terpene cyclases in Trichoderma, responsible for cyclizing geranylgeranyl diphosphate (GGPP) into major diterpenes harzianol I and wickerol A, via heterologous expressions, gene deletion, and in vitro assays. TriDTCs represent a brand new class of terpene cyclases, lacking known motifs and diverging from all known enzymes. Mechanistically, TriDTCs likely employ a unique DxxDxxxD aspartate triad for cyclization initiation, a critical valine residue modulating product specificity, and “gatekeeper” residues for activity. Phylogenetic analysis shows TriDTCs have a narrow distribution in three fungal genera and are highly functionally specific within Trichoderma, suggesting a genus-specific acquisition and independent evolution. Functional studies implicated TriDTCs in fungal survival strategies by regulating formation of resistant propagules (chlamydospore in Trichoderma, sclerotia in Aspergillus oryzae). These findings expand the knowledge of terpene cyclase diversity and biological significance, herald a strategy to enhance Trichoderma’s biocontrol efficacy, and open avenues for pharmacological investigation of these diterpenoids.https://doi.org/10.1038/s41467-025-63055-4 |
| spellingShingle | Min-Jie Yang De-Sen Li Hua-Qin Deng Wen-Yuan Li Xin-Yu Zheng Jonathan Gershenzon Xue-Mei Niu Yan Liu Sheng-Hong Li Noncanonical terpene cyclases for the biosynthesis of diterpenoids regulating chlamydospore formation in plant-associated Trichoderma Nature Communications |
| title | Noncanonical terpene cyclases for the biosynthesis of diterpenoids regulating chlamydospore formation in plant-associated Trichoderma |
| title_full | Noncanonical terpene cyclases for the biosynthesis of diterpenoids regulating chlamydospore formation in plant-associated Trichoderma |
| title_fullStr | Noncanonical terpene cyclases for the biosynthesis of diterpenoids regulating chlamydospore formation in plant-associated Trichoderma |
| title_full_unstemmed | Noncanonical terpene cyclases for the biosynthesis of diterpenoids regulating chlamydospore formation in plant-associated Trichoderma |
| title_short | Noncanonical terpene cyclases for the biosynthesis of diterpenoids regulating chlamydospore formation in plant-associated Trichoderma |
| title_sort | noncanonical terpene cyclases for the biosynthesis of diterpenoids regulating chlamydospore formation in plant associated trichoderma |
| url | https://doi.org/10.1038/s41467-025-63055-4 |
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