Last week, the SusChem announced that Dr. Jordi Soler received the XVI Premios SusChem Jóvenes Investigadores Químicos categoria Investiga for his best scientific publication on Engineered cytochrome P450 for direct arylalkene-to-ketone oxidation via highly reactive carbocatión intermediates. This prize is rewarded annually to young Spanish researchers. The SusChem Young Chemical Researchers Awards aim to recognize, encourage and promote scientific and informative activity among young chemical researchers, as well as to promote, develop and disseminate the discipline of Chemistry, both in its pure science aspect and in that of its applications in Spain. Dr. Jordi Soler defended his PhD thesis supervised by Prof. Sílvia Osuna and Dr. Marc Garcia-Borràs from IQCC in 2023.
The publication was:
Sebastian Gergel, Jordi Soler, Alina Klein, KaiH. Schülke, Bernhard Hauer, Marc Garcia-Borràs, StephanC. Hammer
Engineered cytochrome P450 for direct arylalkene-to-ketone oxidation via highly reactive carbocation intermediates
Nat Catal, 2023, 6, 606-617
DOI: 10.1038/s41929-023-00979-4
This collaborative work has been carried out by Sebastian Gergel (web-lab experiments, Bielefeld University) and by Dr. Jordi Soler (computational analysis, IQCC-University of Girona) as co-first authors. Dr. Marc Garcia-Borràs (IQCC- UdG) and Stephan Hammer (BU) leadered the project.
Ketones are crucial intermediates in synthesis and frequent moieties in many products. The direct regioselective synthesis of ketones from internal alkenes could simplify synthetic routes and solve a long-standing challenge in catalysis. Current synthetic strategies make use of boron and palladium catalysts, which are inefficient and toxic. Here we report the laboratory evolution of a cytochrome P450 enzyme for the direct oxidation of internal arylalkenes to ketones with several thousand turnovers. This evolved ketone synthase benefits from 15 crucial mutations, most of them distal to the active site. Computational analysis revealed that all these mutations collaborate to generate and tame a highly reactive carbocation intermediate. This is achieved through a confined, rigid, and geometrically and electrostatically preorganized active site. The engineered enzyme exploits a metal–oxo species for ketone synthesis and enables various challenging alkene functionalization reactions. This includes the catalytic, enantioselective oxidation of internal alkenes to ketones and formal asymmetric hydrofunctionalizations of internal alkenes in combination with other biocatalysts.
Congratulations Jordi!
Girona, July 16, 2024
For more info: ges.iqcc@udg.edu