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An Engineered E. coli Strain for Direct in Vivo Fluorination
Author(s) -
Markakis Konstantinos,
Lowe Phillip T.,
DavisonGates Liam,
O'Hagan David,
Rosser Susan J.,
Elfick Alistair
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000051
Subject(s) - escherichia coli , efflux , chemistry , protein engineering , biochemistry , fluorine , bacteria , streptomyces , enzyme , reagent , combinatorial chemistry , biology , organic chemistry , genetics , gene
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.