A Collaborative Proposal in Redox Biocatalysis: Focusing on Peroxygenases and Beyond

• Grant number: 24/09456-1
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Leticia Maria Zanphorlin
• Grantee: Leticia Maria Zanphorlin
• Principal researcher abroad: Frank Hollmann
• Institution abroad: Delft University of Technology (TU Delft), Netherlands
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated research grant: 24/01393-0 - Mechanisms of (regio)-chemoselectivity of iron-enzymes that catalyze the non-canonical decarboxylation of fatty acids in hydrocarbon biosynthesis, AP.R

Abstract

Building a bio-based economy is one of the main challenges of society in the 21st century, in order to mitigate climate change and diminish our dependence on fossil resources for the production of energy, materials and chemicals. Among the many proposed approaches, technologies based on the biological conversion of residues from agricultural and industrial resources are a promising solution for manufacturing various compounds and added-value products. Industrial biotechnology offers huge potential for economic growth across a wide range of market and industry sectors by greener and cleaner manufacturing processes, as well as proffering opportunities for residues utilization and new products that will benefit society. In this regard, Dr. Zanphorlin from LNBR/CNPEM and Dr. Hollmann from TU Delft, along with their respective research groups, have devoted significant efforts to discovering, understanding the mechanisms, and applying oxidoreductases such as monoxygenases and peroxygenases. These enzymes play a crucial role in catalyzing the oxyfunctionalization of non-activated C-H, C-C, or C=C bonds, leading to the generation of molecules with drop-in specificities or serving as precursors for a diverse array of value-added products. This capability opens up avenues for the synthesis of various compounds with applications across multiple industries, further highlighting the importance of these enzymes in biocatalysis. In this sense, the collaborative project aims to utilize the enzymes developed by both groups to construct enzyme cascades, enabling the production of epoxides. Epoxides are a valuable class of compounds across the pharmaceutical and fragrance industries. They can be found in medicinal compounds such as carfilzomib (an anticancer agent) and troleandomycin (a macrolide antibiotic). The reactivity of epoxides toward a broad range of nucleophiles makes them versatile intermediates. This enzyme cascade will utilize as "feedstock" the alkenes produced by a robust and highly efficient peroxygenase P450 discovered (PNAS, 2023) by LNBR/CNPEM. Throughout this project, the enzyme cascades will be evaluated through in silico experiments to assess thermodynamic aspects and establish initial parameters for functioning. Ultimately, we also plan to conduct in-person missions over the course of a year, facilitating researcher exchanges to discuss results and strategize the development of a structured follow-up project. This inaugural collaboration between LNBR and TU Delft holds numerous benefits. Firstly, it establishes a new scientific interaction that may extend to other projects and involve researchers from both institutes. Additionally, students affiliated with each group could also be engaged, thereby incorporating new knowledge and capabilities into the collaboration. From a broader perspective, this project has the potential to contribute to a more sustainable society by developing and evaluating new bio-based technologies for petroleum substitution. Through this initiative, we aim to advance the field of biocatalysis and pave the way for more environmentally friendly and economically viable solutions. (AU)