Gene duplication and clustering underlie the conservation and diversification of benzylisoquinoline alkaloid biosynthesis in plants
Abstract Benzylisoquinoline alkaloids (BIAs), comprising ~2500 compounds with pharmacological significance, are well-studied in Ranunculales but poorly understood in Magnoliids, an early-diverging angiosperm group. This study characterizes key enzymes in Houttuynia cordata—including 6-OMT, NMT, CYP8...
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| Format: | Article |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-63175-x |
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| author | Changheng Shan Xuan Zhou Jiaojiao Zhu Aatif Rashid Jianhua Wang Ning An Changjian Zhang Wenjuan Ji Baosong Cai Ke Wu Sheng Wang Zhenhua Liu |
| author_facet | Changheng Shan Xuan Zhou Jiaojiao Zhu Aatif Rashid Jianhua Wang Ning An Changjian Zhang Wenjuan Ji Baosong Cai Ke Wu Sheng Wang Zhenhua Liu |
| author_sort | Changheng Shan |
| collection | DOAJ |
| description | Abstract Benzylisoquinoline alkaloids (BIAs), comprising ~2500 compounds with pharmacological significance, are well-studied in Ranunculales but poorly understood in Magnoliids, an early-diverging angiosperm group. This study characterizes key enzymes in Houttuynia cordata—including 6-OMT, NMT, CYP80B, and 4’OMT—that form BIA backbones and uncovers a CYP80G-mediated phenol coupling reaction in isoboldine biosynthesis. Functional analysis reveals conservation of BIA backbone formation genes between Magnoliids and Ranunculales, with evidence of gene duplication and neofunctionalization in H. cordata. Genome-wide analysis identifies dynamic clustering of CYP80B with 4’OMT and 6-OMT genes across angiosperms, reflecting their interlinked biochemical roles in the formation of BIA backbones. These findings suggest that such gene clustering may evolved through biochemical coordination, offering insights into the evolutionary mechanisms behind plant gene cluster formation. The study provides a foundation for understanding BIA biosynthesis across flowering plants and supports synthetic biology strategies to produce high-value BIAs. |
| format | Article |
| id | doaj-art-7459cd8ea4e54d99874d8cfc1fdcf0a6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7459cd8ea4e54d99874d8cfc1fdcf0a62025-08-24T11:39:09ZengNature PortfolioNature Communications2041-17232025-08-0116111010.1038/s41467-025-63175-xGene duplication and clustering underlie the conservation and diversification of benzylisoquinoline alkaloid biosynthesis in plantsChangheng Shan0Xuan Zhou1Jiaojiao Zhu2Aatif Rashid3Jianhua Wang4Ning An5Changjian Zhang6Wenjuan Ji7Baosong Cai8Ke Wu9Sheng Wang10Zhenhua Liu11Shanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong UniversityShanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong UniversityShanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong UniversityShanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong UniversityShanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong UniversityShanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong UniversityShanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong UniversityShanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong UniversityShanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong UniversityShanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong UniversityState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical SciencesShanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong UniversityAbstract Benzylisoquinoline alkaloids (BIAs), comprising ~2500 compounds with pharmacological significance, are well-studied in Ranunculales but poorly understood in Magnoliids, an early-diverging angiosperm group. This study characterizes key enzymes in Houttuynia cordata—including 6-OMT, NMT, CYP80B, and 4’OMT—that form BIA backbones and uncovers a CYP80G-mediated phenol coupling reaction in isoboldine biosynthesis. Functional analysis reveals conservation of BIA backbone formation genes between Magnoliids and Ranunculales, with evidence of gene duplication and neofunctionalization in H. cordata. Genome-wide analysis identifies dynamic clustering of CYP80B with 4’OMT and 6-OMT genes across angiosperms, reflecting their interlinked biochemical roles in the formation of BIA backbones. These findings suggest that such gene clustering may evolved through biochemical coordination, offering insights into the evolutionary mechanisms behind plant gene cluster formation. The study provides a foundation for understanding BIA biosynthesis across flowering plants and supports synthetic biology strategies to produce high-value BIAs.https://doi.org/10.1038/s41467-025-63175-x |
| spellingShingle | Changheng Shan Xuan Zhou Jiaojiao Zhu Aatif Rashid Jianhua Wang Ning An Changjian Zhang Wenjuan Ji Baosong Cai Ke Wu Sheng Wang Zhenhua Liu Gene duplication and clustering underlie the conservation and diversification of benzylisoquinoline alkaloid biosynthesis in plants Nature Communications |
| title | Gene duplication and clustering underlie the conservation and diversification of benzylisoquinoline alkaloid biosynthesis in plants |
| title_full | Gene duplication and clustering underlie the conservation and diversification of benzylisoquinoline alkaloid biosynthesis in plants |
| title_fullStr | Gene duplication and clustering underlie the conservation and diversification of benzylisoquinoline alkaloid biosynthesis in plants |
| title_full_unstemmed | Gene duplication and clustering underlie the conservation and diversification of benzylisoquinoline alkaloid biosynthesis in plants |
| title_short | Gene duplication and clustering underlie the conservation and diversification of benzylisoquinoline alkaloid biosynthesis in plants |
| title_sort | gene duplication and clustering underlie the conservation and diversification of benzylisoquinoline alkaloid biosynthesis in plants |
| url | https://doi.org/10.1038/s41467-025-63175-x |
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