Transaminase-catalyzed sequential hydrodefluorinations of perfluorinated methylene groups

Biocatalysis represents a particularly promising approach for the degradation of recalcitrant fluorochemicals. However, the enzymatic activation of perfluorinated methylene groups remains a challenge, primarily due to the increase in C-F bond strength that correlates with the number of fluorine atoms attached to a single carbon atom. Here, we describe a new-to-nature hydrodefluorination reaction catalyzed by engineered transaminases for the biodegradation of difluorinated fused-ring ketones. Remarkable defluorination efficiency was achieved in most cases by employing a slight excess of 2-PrNH₂ as amine donor. Experimental results provide conclusive evidence that the catalytic process commences with a reversible transamination step. The comprehensive examination of this promiscuous reaction provides constructive guidance for the development of emerging biocatalytic strategies, thereby facilitating the biodegradation of polyfluorinated compounds and contributing to environmental sustainability.