An engineered E. coli strain for direct in vivo fluorination
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Selectively fluorinated compounds are found frequently in pharmaceutical and agrochemical products where currently 25–30 % of optimised compounds emerge from development containing at least one fluorine atom. There are many methods for the 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 Streptomyces cattleya, is engineered into Escherichia coli in such a manner that 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 that has the potential for future engineering of more elaborate fluorometabolites.
Markakis , K , Lowe , P T , Davison-Gates , L , O'Hagan , D , Rosser , S J & Elfick , A 2020 , ' An engineered E. coli strain for direct in vivo fluorination ' , ChemBioChem , vol. Early View . https://doi.org/10.1002/cbic.202000051
Copyright © 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1002/cbic.202000051
DescriptionThis work was funded by the Industrial Biotechnology Innovation Centre (IBioIC) with support from GlaxoSmithKline, and also the EU Horizon 2020 (Sinfonia consortia).
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