Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines
Abstract Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55537-8 |
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| author | Wenxue Wang Peng Wang Chuanteng Ma Kang Li Zian Wang Yuting Liu Lu Wang Guojian Zhang Qian Che Tianjiao Zhu Yuzhong Zhang Dehai Li |
| author_facet | Wenxue Wang Peng Wang Chuanteng Ma Kang Li Zian Wang Yuting Liu Lu Wang Guojian Zhang Qian Che Tianjiao Zhu Yuzhong Zhang Dehai Li |
| author_sort | Wenxue Wang |
| collection | DOAJ |
| description | Abstract Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylallylation on the imidazole moiety in the biosynthesis of aurantiamine. Biochemical assays validate that AuraA could accept both cyclo-(L-Val-L-His) and cyclo-(L-Val-DH-His) as substrates, while the prenylation modes are completely different, yielding C2-regular and C5-reverse products, respectively. Cryo-electron microscopy analysis of AuraA and its two ternary complex structures reveal two distinct modes for receptor binding, demonstrating a tolerance for altered orientations of highly similar receptors. The mutation experiments further demonstrate the promiscuity of AuraA towards imidazole-C-dimethylallylation. In this work, we also characterize a case of AuraA mutant-catalyzed dimethylallylation of imidazole moiety, offering available structural insights into the utilization and engineering of dimethylallyl tryptophan synthase family prenyltransferases. |
| format | Article |
| id | doaj-art-9038966b01b24f9e8b8b59f603840aca |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9038966b01b24f9e8b8b59f603840aca2025-01-05T12:39:48ZengNature PortfolioNature Communications2041-17232025-01-0116111010.1038/s41467-024-55537-8Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazinesWenxue Wang0Peng Wang1Chuanteng Ma2Kang Li3Zian Wang4Yuting Liu5Lu Wang6Guojian Zhang7Qian Che8Tianjiao Zhu9Yuzhong Zhang10Dehai Li11Key Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of ChinaMOE Key Laboratory of Evolution and Marine Biodiversity, Frontiers Science Center for Deep Ocean Multispheres and Earth System & College of Marine Life Sciences, Ocean University of ChinaKey Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of ChinaMOE Key Laboratory of Evolution and Marine Biodiversity, Frontiers Science Center for Deep Ocean Multispheres and Earth System & College of Marine Life Sciences, Ocean University of ChinaKey Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of ChinaKey Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of ChinaKey Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of ChinaKey Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of ChinaKey Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of ChinaKey Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of ChinaLaboratory for Marine Drugs and Bioproducts & Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology CenterKey Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of ChinaAbstract Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylallylation on the imidazole moiety in the biosynthesis of aurantiamine. Biochemical assays validate that AuraA could accept both cyclo-(L-Val-L-His) and cyclo-(L-Val-DH-His) as substrates, while the prenylation modes are completely different, yielding C2-regular and C5-reverse products, respectively. Cryo-electron microscopy analysis of AuraA and its two ternary complex structures reveal two distinct modes for receptor binding, demonstrating a tolerance for altered orientations of highly similar receptors. The mutation experiments further demonstrate the promiscuity of AuraA towards imidazole-C-dimethylallylation. In this work, we also characterize a case of AuraA mutant-catalyzed dimethylallylation of imidazole moiety, offering available structural insights into the utilization and engineering of dimethylallyl tryptophan synthase family prenyltransferases.https://doi.org/10.1038/s41467-024-55537-8 |
| spellingShingle | Wenxue Wang Peng Wang Chuanteng Ma Kang Li Zian Wang Yuting Liu Lu Wang Guojian Zhang Qian Che Tianjiao Zhu Yuzhong Zhang Dehai Li Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines Nature Communications |
| title | Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines |
| title_full | Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines |
| title_fullStr | Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines |
| title_full_unstemmed | Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines |
| title_short | Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines |
| title_sort | characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole containing diketopiperazines |
| url | https://doi.org/10.1038/s41467-024-55537-8 |
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