Custom tuning of Rieske oxygenase reactivity
Abstract Rieske oxygenases use a Rieske-type [2Fe-2S] cluster and a mononuclear iron center to initiate a range of chemical transformations. However, few details exist regarding how this catalytic scaffold can be predictively tuned to catalyze divergent reactions. Therefore, in this work, using a co...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41428-x |
| _version_ | 1797558684283305984 |
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| author | Jiayi Tian Jianxin Liu Madison Knapp Patrick H. Donnan David G. Boggs Jennifer Bridwell-Rabb |
| author_facet | Jiayi Tian Jianxin Liu Madison Knapp Patrick H. Donnan David G. Boggs Jennifer Bridwell-Rabb |
| author_sort | Jiayi Tian |
| collection | DOAJ |
| description | Abstract Rieske oxygenases use a Rieske-type [2Fe-2S] cluster and a mononuclear iron center to initiate a range of chemical transformations. However, few details exist regarding how this catalytic scaffold can be predictively tuned to catalyze divergent reactions. Therefore, in this work, using a combination of structural analyses, as well as substrate and rational protein-based engineering campaigns, we elucidate the architectural trends that govern catalytic outcome in the Rieske monooxygenase TsaM. We identify structural features that permit a substrate to be functionalized by TsaM and pinpoint active-site residues that can be targeted to manipulate reactivity. Exploiting these findings allowed for custom tuning of TsaM reactivity: substrates are identified that support divergent TsaM-catalyzed reactions and variants are created that exclusively catalyze dioxygenation or sequential monooxygenation chemistry. Importantly, we further leverage these trends to tune the reactivity of additional monooxygenase and dioxygenase enzymes, and thereby provide strategies to custom tune Rieske oxygenase reaction outcomes. |
| first_indexed | 2024-03-10T17:34:37Z |
| format | Article |
| id | doaj.art-d55444b4d4374be186eeea05cd5842fe |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:34:37Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d55444b4d4374be186eeea05cd5842fe2023-11-20T09:54:12ZengNature PortfolioNature Communications2041-17232023-09-0114112010.1038/s41467-023-41428-xCustom tuning of Rieske oxygenase reactivityJiayi Tian0Jianxin Liu1Madison Knapp2Patrick H. Donnan3David G. Boggs4Jennifer Bridwell-Rabb5Department of Chemistry, University of MichiganDepartment of Chemistry, University of MichiganDepartment of Chemistry, University of MichiganDepartment of Chemistry, University of MichiganDepartment of Chemistry, University of MichiganDepartment of Chemistry, University of MichiganAbstract Rieske oxygenases use a Rieske-type [2Fe-2S] cluster and a mononuclear iron center to initiate a range of chemical transformations. However, few details exist regarding how this catalytic scaffold can be predictively tuned to catalyze divergent reactions. Therefore, in this work, using a combination of structural analyses, as well as substrate and rational protein-based engineering campaigns, we elucidate the architectural trends that govern catalytic outcome in the Rieske monooxygenase TsaM. We identify structural features that permit a substrate to be functionalized by TsaM and pinpoint active-site residues that can be targeted to manipulate reactivity. Exploiting these findings allowed for custom tuning of TsaM reactivity: substrates are identified that support divergent TsaM-catalyzed reactions and variants are created that exclusively catalyze dioxygenation or sequential monooxygenation chemistry. Importantly, we further leverage these trends to tune the reactivity of additional monooxygenase and dioxygenase enzymes, and thereby provide strategies to custom tune Rieske oxygenase reaction outcomes.https://doi.org/10.1038/s41467-023-41428-x |
| spellingShingle | Jiayi Tian Jianxin Liu Madison Knapp Patrick H. Donnan David G. Boggs Jennifer Bridwell-Rabb Custom tuning of Rieske oxygenase reactivity Nature Communications |
| title | Custom tuning of Rieske oxygenase reactivity |
| title_full | Custom tuning of Rieske oxygenase reactivity |
| title_fullStr | Custom tuning of Rieske oxygenase reactivity |
| title_full_unstemmed | Custom tuning of Rieske oxygenase reactivity |
| title_short | Custom tuning of Rieske oxygenase reactivity |
| title_sort | custom tuning of rieske oxygenase reactivity |
| url | https://doi.org/10.1038/s41467-023-41428-x |
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