Structural and functional investigations of syn-copalyl diphosphate synthase from Oryza sativa
Abstract The large superfamily of labdane-related diterpenoids is defined by the cyclization of linear geranylgeranyl pyrophosphate (GGPP), catalyzed by copalyl diphosphate synthases (CPSs) to form the basic decalin core, the copalyl diphosphates (CPPs). Three stereochemically distinct CPPs have bee...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-023-01042-w |
| _version_ | 1797630356719927296 |
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| author | Xiaoli Ma Haifeng Xu Yuru Tong Yunfeng Luo Qinghua Dong Tao Jiang |
| author_facet | Xiaoli Ma Haifeng Xu Yuru Tong Yunfeng Luo Qinghua Dong Tao Jiang |
| author_sort | Xiaoli Ma |
| collection | DOAJ |
| description | Abstract The large superfamily of labdane-related diterpenoids is defined by the cyclization of linear geranylgeranyl pyrophosphate (GGPP), catalyzed by copalyl diphosphate synthases (CPSs) to form the basic decalin core, the copalyl diphosphates (CPPs). Three stereochemically distinct CPPs have been found in plants, namely (+)-CPP, ent-CPP and syn-CPP. Here, we used X-ray crystallography and cryo-EM methods to describe different oligomeric structures of a syn-copalyl diphosphate synthase from Oryza sativa (OsCyc1), and provided a cryo-EM structure of OsCyc1D367A mutant in complex with the substrate GGPP. Further analysis showed that tetramers are the dominant form of OsCyc1 in solution and are not necessary for enzyme activity in vitro. Through rational design, we identified an OsCyc1 mutant that can generate ent-CPP in addition to syn-CPP. Our work provides a structural and mechanistic basis for comparing different CPSs and paves the way for further enzyme design to obtain diterpene derivatives with specific chirality. |
| first_indexed | 2024-03-11T11:07:13Z |
| format | Article |
| id | doaj.art-1b7cebd16a274e3994bc38ccbda50883 |
| institution | Directory Open Access Journal |
| issn | 2399-3669 |
| language | English |
| last_indexed | 2024-03-11T11:07:13Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj.art-1b7cebd16a274e3994bc38ccbda508832023-11-12T12:09:27ZengNature PortfolioCommunications Chemistry2399-36692023-11-016111410.1038/s42004-023-01042-wStructural and functional investigations of syn-copalyl diphosphate synthase from Oryza sativaXiaoli Ma0Haifeng Xu1Yuru Tong2Yunfeng Luo3Qinghua Dong4Tao Jiang5National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesSchool of Pharmaceutical Sciences, Capital Medical UniversitySchool of Traditional Chinese Medicine, Capital Medical UniversityNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesAbstract The large superfamily of labdane-related diterpenoids is defined by the cyclization of linear geranylgeranyl pyrophosphate (GGPP), catalyzed by copalyl diphosphate synthases (CPSs) to form the basic decalin core, the copalyl diphosphates (CPPs). Three stereochemically distinct CPPs have been found in plants, namely (+)-CPP, ent-CPP and syn-CPP. Here, we used X-ray crystallography and cryo-EM methods to describe different oligomeric structures of a syn-copalyl diphosphate synthase from Oryza sativa (OsCyc1), and provided a cryo-EM structure of OsCyc1D367A mutant in complex with the substrate GGPP. Further analysis showed that tetramers are the dominant form of OsCyc1 in solution and are not necessary for enzyme activity in vitro. Through rational design, we identified an OsCyc1 mutant that can generate ent-CPP in addition to syn-CPP. Our work provides a structural and mechanistic basis for comparing different CPSs and paves the way for further enzyme design to obtain diterpene derivatives with specific chirality.https://doi.org/10.1038/s42004-023-01042-w |
| spellingShingle | Xiaoli Ma Haifeng Xu Yuru Tong Yunfeng Luo Qinghua Dong Tao Jiang Structural and functional investigations of syn-copalyl diphosphate synthase from Oryza sativa Communications Chemistry |
| title | Structural and functional investigations of syn-copalyl diphosphate synthase from Oryza sativa |
| title_full | Structural and functional investigations of syn-copalyl diphosphate synthase from Oryza sativa |
| title_fullStr | Structural and functional investigations of syn-copalyl diphosphate synthase from Oryza sativa |
| title_full_unstemmed | Structural and functional investigations of syn-copalyl diphosphate synthase from Oryza sativa |
| title_short | Structural and functional investigations of syn-copalyl diphosphate synthase from Oryza sativa |
| title_sort | structural and functional investigations of syn copalyl diphosphate synthase from oryza sativa |
| url | https://doi.org/10.1038/s42004-023-01042-w |
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