Leveraging core enzyme structures for microbiota targeted functional regulation: Urease as an example
Abstract Microbial communities play critical roles in various ecosystems. Despite extensive research on the taxonomic and functional diversity of microbial communities, effective approaches to regulate targeted microbial functions remain limited. Here, we present an innovative methodology that integ...
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| Format: | Article |
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Wiley
2025-06-01
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| Series: | iMeta |
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| Online Access: | https://doi.org/10.1002/imt2.70032 |
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| author | Shengguo Zhao Huiyue Zhong Yue He Xiaojiao Li Li Zhu Zhanbo Xiong Xiaoyin Zhang Nan Zheng Diego P. Morgavi Jiaqi Wang |
| author_facet | Shengguo Zhao Huiyue Zhong Yue He Xiaojiao Li Li Zhu Zhanbo Xiong Xiaoyin Zhang Nan Zheng Diego P. Morgavi Jiaqi Wang |
| author_sort | Shengguo Zhao |
| collection | DOAJ |
| description | Abstract Microbial communities play critical roles in various ecosystems. Despite extensive research on the taxonomic and functional diversity of microbial communities, effective approaches to regulate targeted microbial functions remain limited. Here, we present an innovative methodology that integrates core enzyme identification, protein structural characterization, regulator virtual screening, and functional validation to achieve precise microbiome functional regulation. As a proof of concept, we focused on the regulation of urea decomposition by the rumen microbiota in ruminants. Through metagenomic analysis, we identified the core urease gene and its corresponding microbial genome (MAG257) affiliated with the unclassified Succinivibrionaceae, and reconstructed its complete gene cluster. Structural analysis of the urease catalytic subunit (UreC) via cryo‐electron microscopy (cryo‐EM) revealed detailed features of its active site, guiding molecular docking studies that identified epiberberine, a natural compound with potent urease inhibitory activity. Validation in a rumen simulation system demonstrated that epiberberine significantly reduced urea decomposition and enhanced nitrogen utilization. This study establishes a robust framework that combines structural biology and computational screening to achieve targeted microbiome functional regulation, offering a promising tool for microbiome engineering and broader applications in animal productivity, human health, environmental improvement, and biotechnology. |
| format | Article |
| id | doaj-art-6091fd0d07264818a6f4a9bc583d3af3 |
| institution | OA Journals |
| issn | 2770-596X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | iMeta |
| spelling | doaj-art-6091fd0d07264818a6f4a9bc583d3af32025-08-20T02:05:23ZengWileyiMeta2770-596X2025-06-0143n/an/a10.1002/imt2.70032Leveraging core enzyme structures for microbiota targeted functional regulation: Urease as an exampleShengguo Zhao0Huiyue Zhong1Yue He2Xiaojiao Li3Li Zhu4Zhanbo Xiong5Xiaoyin Zhang6Nan Zheng7Diego P. Morgavi8Jiaqi Wang9Key State Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences Chinese Academy of Agricultural Sciences Beijing ChinaKey State Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences Chinese Academy of Agricultural Sciences Beijing ChinaKey State Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences Chinese Academy of Agricultural Sciences Beijing ChinaKey State Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences Chinese Academy of Agricultural Sciences Beijing ChinaElectron Microscopy Centre Lanzhou University Lanzhou ChinaKey State Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences Chinese Academy of Agricultural Sciences Beijing ChinaKey State Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences Chinese Academy of Agricultural Sciences Beijing ChinaKey State Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences Chinese Academy of Agricultural Sciences Beijing ChinaUniversité Clermont Auvergne, INRAE, VetAgro Sup, UMR Herbivores, Saint‐Genès‐Champanelle Clermont‐Ferrand FranceKey State Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences Chinese Academy of Agricultural Sciences Beijing ChinaAbstract Microbial communities play critical roles in various ecosystems. Despite extensive research on the taxonomic and functional diversity of microbial communities, effective approaches to regulate targeted microbial functions remain limited. Here, we present an innovative methodology that integrates core enzyme identification, protein structural characterization, regulator virtual screening, and functional validation to achieve precise microbiome functional regulation. As a proof of concept, we focused on the regulation of urea decomposition by the rumen microbiota in ruminants. Through metagenomic analysis, we identified the core urease gene and its corresponding microbial genome (MAG257) affiliated with the unclassified Succinivibrionaceae, and reconstructed its complete gene cluster. Structural analysis of the urease catalytic subunit (UreC) via cryo‐electron microscopy (cryo‐EM) revealed detailed features of its active site, guiding molecular docking studies that identified epiberberine, a natural compound with potent urease inhibitory activity. Validation in a rumen simulation system demonstrated that epiberberine significantly reduced urea decomposition and enhanced nitrogen utilization. This study establishes a robust framework that combines structural biology and computational screening to achieve targeted microbiome functional regulation, offering a promising tool for microbiome engineering and broader applications in animal productivity, human health, environmental improvement, and biotechnology.https://doi.org/10.1002/imt2.70032coreepiberberinefunctionmicrobiomeprotein structurerumen |
| spellingShingle | Shengguo Zhao Huiyue Zhong Yue He Xiaojiao Li Li Zhu Zhanbo Xiong Xiaoyin Zhang Nan Zheng Diego P. Morgavi Jiaqi Wang Leveraging core enzyme structures for microbiota targeted functional regulation: Urease as an example iMeta core epiberberine function microbiome protein structure rumen |
| title | Leveraging core enzyme structures for microbiota targeted functional regulation: Urease as an example |
| title_full | Leveraging core enzyme structures for microbiota targeted functional regulation: Urease as an example |
| title_fullStr | Leveraging core enzyme structures for microbiota targeted functional regulation: Urease as an example |
| title_full_unstemmed | Leveraging core enzyme structures for microbiota targeted functional regulation: Urease as an example |
| title_short | Leveraging core enzyme structures for microbiota targeted functional regulation: Urease as an example |
| title_sort | leveraging core enzyme structures for microbiota targeted functional regulation urease as an example |
| topic | core epiberberine function microbiome protein structure rumen |
| url | https://doi.org/10.1002/imt2.70032 |
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