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Generoso, Wesley Cardoso ; Alvarenga, Alana Helen Santana ; Simoes, Isabelle Taira ; Miyamoto, Renan Yuji ; de Melo, Ricardo Rodrigues ; Guilherme, Ederson Paulo Xavier ; Mandelli, Fernanda ; Santos, Clelton Aparecido ; Prata, Rafaela ; dos Santos, Camila Ramos ; Colombari, Felippe Mariano ; Morais, Mariana Abrahao Bueno ; Fernandes, Rodrigo Pimentel ; Persinoti, Gabriela Felix ; Murakami, Mario Tyago ; Zanphorlin, Leticia Maria

• Tipo de documento: Artigo Científico
• Fonte: NATURE COMMUNICATIONS; v. 16, n. 1, p. 13-pg., 2025-01-22.

Resumo

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 C beta 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. (AU)

• Processo FAPESP: 18/02865-2 - Investigação molecular de novas xilose isomerases para aplicação na fermentação de materiais lignocelulósicos
• Beneficiário: Renan Yuji Miyamoto
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 19/08855-1 - Novos mecanismos de P450: uma estratégia enzimática para a produção de hidrocarbonetos renováveis
• Beneficiário: Leticia Maria Zanphorlin
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/14410-2 - Estudo de enzimas P450 da família CYP152 capazes de promover a descarboxilação de ácidos graxos
• Beneficiário: Isabelle Taira Simões
• Modalidade de apoio: Bolsas no Brasil - Mestrado