An engineered E. coli strain for direct in vivo fluorination

Selectively fluorinated compounds are found frequently in pharmaceutical and agrochemical products where currently 25‐30% of optimized compounds emerge from development containing at least one fluorine atom. There are many methods for site specific introduction of fluorine, but all are chemical and they often use environmentally challenging reagents. Biochemical processes for C‐F bond formation are attractive but they are extremely rare. In this work the fluorinase enzyme, originally identified from the actinomycete bacterium S. cattleya, is engineered into E. coli in a manner where the organism is able to produce 5’‐fluorodeoxyadenosine (5’‐FDA) from S‐adenosyl‐L‐methionine (SAM) and fluoride in live E. coli cells. Success required the introduction of a SAM transporter and deletion of the endogenous fluoride efflux capacity, in order to generate an E. coli host which has potential for future engineering of more elaborate fluorometabolites.