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An engineered E. coli strain for direct in vivo fluorination

Research output: Contribution to journalArticle

DOI

Open Access Status

  • Embargoed (until 3/03/21)

Author(s)

Konstantinos Markakis, Phillip T. Lowe, Liam Davison-Gates, David O'Hagan, Susan J. Rosser, Alistair Elfick

School/Research organisations

Abstract

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.
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Details

Original languageEnglish
JournalChemBioChem
VolumeEarly View
Early online date3 Mar 2020
DOIs
Publication statusE-pub ahead of print - 3 Mar 2020

    Research areas

  • Escherichia coli, Fluoride channels, Fluorinases, Halogenations, SAM transporters

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