Engineering synthetic metabolisms for biohalogenation

The non-pathogenic soil bacterium P. putida is highly tolerant to stressful conditions and toxic chemicals, traits stemming from its unique metabolic architecture. For these reasons, we have adopted this bacterium as the host to engineer novel biochemistries leading to new-to-Nature fine chemicals. We focus on establishing halogenation of organic molecules for the biosynthesis of organofluorines, i.e. molecules with one or more C–F bonds in their structure. Organofluorines are of extraordinary importance in the pharmaceutical industry, and a third of the drugs currently in clinical trials contain C–F bonds―but their production, strictly dependent on traditional chemistry, is often difficult to achieve because of the electronegativity of F and its high reactivity. The extreme chemical properties of F limited the evolution of natural biochemical pathways leading to fluorometabolites. However, fluorinase, an enzyme found in Streptomyces cattleya, is known to catalyze the formation of a fluorinated nucleoside. Using a combination of synthetic biology, protein engineering and metabolic engineering approaches, we are establishing P. putida KT2440 as a cell platform for the sustainable production of organofluorines.