Coordinated conformational changes in P450 decarboxylases enable hydrocarbons production from renewable feedstocks
Abstract Fatty acid peroxygenases have emerged as promising biocatalysts for hydrocarbon biosynthesis due to their ability to perform C-C scission, producing olefins - key building blocks for sustainable materials and fuels. These enzymes operate through non-canonical and complex mechanisms that yie...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56256-4 |
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| author | Wesley Cardoso Generoso Alana Helen Santana Alvarenga Isabelle Taira Simões Renan Yuji Miyamoto Ricardo Rodrigues de Melo Ederson Paulo Xavier Guilherme Fernanda Mandelli Clelton Aparecido Santos Rafaela Prata Camila Ramos dos Santos Felippe Mariano Colombari Mariana Abrahão Bueno Morais Rodrigo Pimentel Fernandes Gabriela Felix Persinoti Mario Tyago Murakami Leticia Maria Zanphorlin |
| author_facet | Wesley Cardoso Generoso Alana Helen Santana Alvarenga Isabelle Taira Simões Renan Yuji Miyamoto Ricardo Rodrigues de Melo Ederson Paulo Xavier Guilherme Fernanda Mandelli Clelton Aparecido Santos Rafaela Prata Camila Ramos dos Santos Felippe Mariano Colombari Mariana Abrahão Bueno Morais Rodrigo Pimentel Fernandes Gabriela Felix Persinoti Mario Tyago Murakami Leticia Maria Zanphorlin |
| author_sort | Wesley Cardoso Generoso |
| collection | DOAJ |
| description | Abstract Fatty acid peroxygenases have emerged as promising biocatalysts for hydrocarbon biosynthesis due to their ability to perform C-C scission, producing olefins - key building blocks for sustainable materials and fuels. These enzymes operate through non-canonical and complex mechanisms that yield a bifurcated chemoselectivity between hydroxylation and decarboxylation. In this study, we elucidate structural features in P450 decarboxylases that enable the catalysis of unsaturated substrates, expanding the mechanistic pathways for decarboxylation reaction. Combining X-ray crystallography, molecular dynamics simulations, and machine learning, we have identified intricate molecular rearrangements within the active site that enable the Cβ atom of the substrate to approach the heme iron, thereby promoting oleate decarboxylation. Furthermore, we demonstrate that the absence of the aromatic residue in the Phe-His-Arg triad preserves chemoselectivity for alkenes, providing a distinct perspective on the molecular determinants of decarboxylation activity. Ultimately, these findings enable the sustainable production of biohydrocarbons from industrial feedstocks. |
| format | Article |
| id | doaj-art-af065e4052584a4d96fe1563bdd8e9ab |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-af065e4052584a4d96fe1563bdd8e9ab2025-01-26T12:42:44ZengNature PortfolioNature Communications2041-17232025-01-0116111310.1038/s41467-025-56256-4Coordinated conformational changes in P450 decarboxylases enable hydrocarbons production from renewable feedstocksWesley Cardoso Generoso0Alana Helen Santana Alvarenga1Isabelle Taira Simões2Renan Yuji Miyamoto3Ricardo Rodrigues de Melo4Ederson Paulo Xavier Guilherme5Fernanda Mandelli6Clelton Aparecido Santos7Rafaela Prata8Camila Ramos dos Santos9Felippe Mariano Colombari10Mariana Abrahão Bueno Morais11Rodrigo Pimentel Fernandes12Gabriela Felix Persinoti13Mario Tyago Murakami14Leticia Maria Zanphorlin15Brazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsSinochem Petróleo Brasil LtdaBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsBrazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and MaterialsAbstract Fatty acid peroxygenases have emerged as promising biocatalysts for hydrocarbon biosynthesis due to their ability to perform C-C scission, producing olefins - key building blocks for sustainable materials and fuels. These enzymes operate through non-canonical and complex mechanisms that yield a bifurcated chemoselectivity between hydroxylation and decarboxylation. In this study, we elucidate structural features in P450 decarboxylases that enable the catalysis of unsaturated substrates, expanding the mechanistic pathways for decarboxylation reaction. Combining X-ray crystallography, molecular dynamics simulations, and machine learning, we have identified intricate molecular rearrangements within the active site that enable the Cβ atom of the substrate to approach the heme iron, thereby promoting oleate decarboxylation. Furthermore, we demonstrate that the absence of the aromatic residue in the Phe-His-Arg triad preserves chemoselectivity for alkenes, providing a distinct perspective on the molecular determinants of decarboxylation activity. Ultimately, these findings enable the sustainable production of biohydrocarbons from industrial feedstocks.https://doi.org/10.1038/s41467-025-56256-4 |
| spellingShingle | Wesley Cardoso Generoso Alana Helen Santana Alvarenga Isabelle Taira Simões Renan Yuji Miyamoto Ricardo Rodrigues de Melo Ederson Paulo Xavier Guilherme Fernanda Mandelli Clelton Aparecido Santos Rafaela Prata Camila Ramos dos Santos Felippe Mariano Colombari Mariana Abrahão Bueno Morais Rodrigo Pimentel Fernandes Gabriela Felix Persinoti Mario Tyago Murakami Leticia Maria Zanphorlin Coordinated conformational changes in P450 decarboxylases enable hydrocarbons production from renewable feedstocks Nature Communications |
| title | Coordinated conformational changes in P450 decarboxylases enable hydrocarbons production from renewable feedstocks |
| title_full | Coordinated conformational changes in P450 decarboxylases enable hydrocarbons production from renewable feedstocks |
| title_fullStr | Coordinated conformational changes in P450 decarboxylases enable hydrocarbons production from renewable feedstocks |
| title_full_unstemmed | Coordinated conformational changes in P450 decarboxylases enable hydrocarbons production from renewable feedstocks |
| title_short | Coordinated conformational changes in P450 decarboxylases enable hydrocarbons production from renewable feedstocks |
| title_sort | coordinated conformational changes in p450 decarboxylases enable hydrocarbons production from renewable feedstocks |
| url | https://doi.org/10.1038/s41467-025-56256-4 |
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