Coordinated conformational changes in P450 decarboxylases enable hydrocarbons production from renewable feedstocks

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 and Leticia Maria Zanphorlin ()
Additional contact information
Wesley Cardoso Generoso: Brazilian Center for Research in Energy and Materials
Alana Helen Santana Alvarenga: Brazilian Center for Research in Energy and Materials
Isabelle Taira Simões: Brazilian Center for Research in Energy and Materials
Renan Yuji Miyamoto: Brazilian Center for Research in Energy and Materials
Ricardo Rodrigues de Melo: Brazilian Center for Research in Energy and Materials
Ederson Paulo Xavier Guilherme: Brazilian Center for Research in Energy and Materials
Fernanda Mandelli: Brazilian Center for Research in Energy and Materials
Clelton Aparecido Santos: Brazilian Center for Research in Energy and Materials
Rafaela Prata: Brazilian Center for Research in Energy and Materials
Camila Ramos dos Santos: Brazilian Center for Research in Energy and Materials
Felippe Mariano Colombari: Brazilian Center for Research in Energy and Materials
Mariana Abrahão Bueno Morais: Brazilian Center for Research in Energy and Materials
Rodrigo Pimentel Fernandes: Sinochem Petróleo Brasil Ltda
Gabriela Felix Persinoti: Brazilian Center for Research in Energy and Materials
Mario Tyago Murakami: Brazilian Center for Research in Energy and Materials
Leticia Maria Zanphorlin: Brazilian Center for Research in Energy and Materials

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56256-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56256-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56256-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().