Coordinated conformational changes in P450 decarboxylases enable hydrocarbons production from renewable feedstocks
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.
Authors
- Leticia Maria Zanphorlin (ORCID: https://orcid.org/0000-0001-7283-5726)
- Wesley Cardoso Generoso (ORCID: https://orcid.org/0000-0002-5923-1458)
- Ricardo Rodrigues de Melo (ORCID: https://orcid.org/0000-0002-0454-1694)
- Renan Y. Miyamoto (ORCID: https://orcid.org/0000-0003-2990-3337)
- Rodrigo Pimentel Fernandes (ORCID: https://orcid.org/0000-0001-7691-0682)
- Gabriela Félix Persinoti (ORCID: https://orcid.org/0000-0002-0975-7283)
- C.R. Santos (ORCID: https://orcid.org/0000-0003-0652-4211)
- Si Li (ORCID: https://orcid.org/0000-0002-5431-1301)
- M.A.B. Morais (ORCID: https://orcid.org/0000-0003-1012-1394)
- M.T. Murakami (ORCID: https://orcid.org/0000-0002-0405-8010)
- F Mandelli (ORCID: https://orcid.org/0000-0003-0891-9241)
- Rafaela Prata (ORCID: https://orcid.org/0000-0001-7419-9196)
- Éderson Paulo Xavier Guilherme (ORCID: https://orcid.org/0000-0002-4048-2759)
- Clelton A. Santos (ORCID: https://orcid.org/0000-0002-6725-8925)
- Isabelle Taira Simões
- Alana Helen Santana Alvarenga
Institutions
- Brazilian Center for Research in Energy and Materials (BR)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-01-22
- DOI
- https://doi.org/10.1038/s41467-025-56256-4
- Citations
- 4
- Primary Topic
- Pharmacogenetics and Drug Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 6.23
Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Ministério da Ciência, Tecnologia e Inovação
- Centro Nacional de Pesquisa em Energia e Materiais
- Laboratório Nacional de Luz Síncrotron
- Laboratório Nacional de Biociências
- Laboratório Nacional de Biorrenováveis