Structure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclization
Abstract An unusual family of bifunctional terpene synthases has been identified in which a prenyltransferase assembles 5-carbon precursors to form C20 geranylgeranyl diphosphate (GGPP), which is then converted into a polycyclic product by a cyclase. Here, we report the cryo-EM structure of a massiv...
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60537-3 |
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| author | Eliott S. Wenger David W. Christianson |
| author_facet | Eliott S. Wenger David W. Christianson |
| author_sort | Eliott S. Wenger |
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| description | Abstract An unusual family of bifunctional terpene synthases has been identified in which a prenyltransferase assembles 5-carbon precursors to form C20 geranylgeranyl diphosphate (GGPP), which is then converted into a polycyclic product by a cyclase. Here, we report the cryo-EM structure of a massive, 495-kD bifunctional terpene synthase, variediene synthase from Emericella variecolor (EvVS). The structure reveals a hexameric prenyltransferase core sandwiched between two triads of cyclases. Surprisingly, GGPP is not channeled intramolecularly from the prenyltransferase to the cyclase, but instead is channeled intermolecularly to a non-native cyclase as indicated by substrate competition experiments. These results inform our understanding of carbon management in the greater family of bifunctional terpene synthases, hundreds of which have been identified in fungi. Using sequence similarity networks, we also report the identification of bifunctional terpene synthases in an animal, Adineta steineri, a bdelloid rotifer indigenous to freshwater environments. |
| format | Article |
| id | doaj-art-93b98a8d69a741708533534fa65ffb69 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-93b98a8d69a741708533534fa65ffb692025-08-20T03:26:43ZengNature PortfolioNature Communications2041-17232025-06-0116111210.1038/s41467-025-60537-3Structure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclizationEliott S. Wenger0David W. Christianson1Department of Chemistry, Roy and Diana Vagelos Laboratories, University of PennsylvaniaDepartment of Chemistry, Roy and Diana Vagelos Laboratories, University of PennsylvaniaAbstract An unusual family of bifunctional terpene synthases has been identified in which a prenyltransferase assembles 5-carbon precursors to form C20 geranylgeranyl diphosphate (GGPP), which is then converted into a polycyclic product by a cyclase. Here, we report the cryo-EM structure of a massive, 495-kD bifunctional terpene synthase, variediene synthase from Emericella variecolor (EvVS). The structure reveals a hexameric prenyltransferase core sandwiched between two triads of cyclases. Surprisingly, GGPP is not channeled intramolecularly from the prenyltransferase to the cyclase, but instead is channeled intermolecularly to a non-native cyclase as indicated by substrate competition experiments. These results inform our understanding of carbon management in the greater family of bifunctional terpene synthases, hundreds of which have been identified in fungi. Using sequence similarity networks, we also report the identification of bifunctional terpene synthases in an animal, Adineta steineri, a bdelloid rotifer indigenous to freshwater environments.https://doi.org/10.1038/s41467-025-60537-3 |
| spellingShingle | Eliott S. Wenger David W. Christianson Structure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclization Nature Communications |
| title | Structure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclization |
| title_full | Structure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclization |
| title_fullStr | Structure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclization |
| title_full_unstemmed | Structure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclization |
| title_short | Structure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclization |
| title_sort | structure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclization |
| url | https://doi.org/10.1038/s41467-025-60537-3 |
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