Functional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone N-oxide
Abstract Chirality plays a critical role in the biochemistry of life and often only one enantiomeric series is observed (homochirality). Only a few natural products have been obtained as racemates, e.g. the signalling molecule valdiazen produced by Burkholderia cenocepacia H111. In this study, we in...
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Nature Portfolio
2024-12-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-024-01372-3 |
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| author | Jiajun Ren Anugraha Mathew María Rodríguez-García Tobias Kohler Olivier Blacque Anthony Linden Leo Eberl Simon Sieber Karl Gademann |
| author_facet | Jiajun Ren Anugraha Mathew María Rodríguez-García Tobias Kohler Olivier Blacque Anthony Linden Leo Eberl Simon Sieber Karl Gademann |
| author_sort | Jiajun Ren |
| collection | DOAJ |
| description | Abstract Chirality plays a critical role in the biochemistry of life and often only one enantiomeric series is observed (homochirality). Only a few natural products have been obtained as racemates, e.g. the signalling molecule valdiazen produced by Burkholderia cenocepacia H111. In this study, we investigated the ham biosynthetic gene cluster and discovered that both the enantiomerically pure (R)-fragin and the racemic valdiazen result from the same pathway. This stereodivergence is based on the unusual heterocyclic intermediate dihydrosydnone N-oxide, as evident from gene knockout, stable isotope feeding experiments, and mass spectrometry experiments. Both non-enzymatic racemisation via keto-enol tautomerisation and enzyme-mediated dynamic kinetic resolution were found to be crucial to this stereodivergent pathway. This novel mechanism underpins the production of configurationally and biologically distinct metabolites from a single gene cluster. Our findings highlight the intricate design of an intertwined biosynthetic pathway and provide a deeper understanding of microbial secondary metabolism related to microbial communication. |
| format | Article |
| id | doaj-art-a37898d17ff14233b2169ff8f97deafe |
| institution | Kabale University |
| issn | 2399-3669 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-a37898d17ff14233b2169ff8f97deafe2024-12-22T12:19:58ZengNature PortfolioCommunications Chemistry2399-36692024-12-01711910.1038/s42004-024-01372-3Functional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone N-oxideJiajun Ren0Anugraha Mathew1María Rodríguez-García2Tobias Kohler3Olivier Blacque4Anthony Linden5Leo Eberl6Simon Sieber7Karl Gademann8Department of Chemistry, University of ZurichDepartment of Plant and Microbial Biology, University of ZurichDepartment of Plant and Microbial Biology, University of ZurichDepartment of Chemistry, University of ZurichDepartment of Chemistry, University of ZurichDepartment of Chemistry, University of ZurichDepartment of Plant and Microbial Biology, University of ZurichDepartment of Chemistry, University of ZurichDepartment of Chemistry, University of ZurichAbstract Chirality plays a critical role in the biochemistry of life and often only one enantiomeric series is observed (homochirality). Only a few natural products have been obtained as racemates, e.g. the signalling molecule valdiazen produced by Burkholderia cenocepacia H111. In this study, we investigated the ham biosynthetic gene cluster and discovered that both the enantiomerically pure (R)-fragin and the racemic valdiazen result from the same pathway. This stereodivergence is based on the unusual heterocyclic intermediate dihydrosydnone N-oxide, as evident from gene knockout, stable isotope feeding experiments, and mass spectrometry experiments. Both non-enzymatic racemisation via keto-enol tautomerisation and enzyme-mediated dynamic kinetic resolution were found to be crucial to this stereodivergent pathway. This novel mechanism underpins the production of configurationally and biologically distinct metabolites from a single gene cluster. Our findings highlight the intricate design of an intertwined biosynthetic pathway and provide a deeper understanding of microbial secondary metabolism related to microbial communication.https://doi.org/10.1038/s42004-024-01372-3 |
| spellingShingle | Jiajun Ren Anugraha Mathew María Rodríguez-García Tobias Kohler Olivier Blacque Anthony Linden Leo Eberl Simon Sieber Karl Gademann Functional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone N-oxide Communications Chemistry |
| title | Functional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone N-oxide |
| title_full | Functional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone N-oxide |
| title_fullStr | Functional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone N-oxide |
| title_full_unstemmed | Functional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone N-oxide |
| title_short | Functional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone N-oxide |
| title_sort | functional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone n oxide |
| url | https://doi.org/10.1038/s42004-024-01372-3 |
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