A fluoride-responsive genetic circuit enables in vivo biofluorination in engineered Pseudomonas putida
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Fluorine is a key element in the synthesis of molecules broadly used in medicine, agriculture and materials. Addition of fluorine to organic structures represents a unique strategy for tuning molecular properties, yet this atom is rarely found in Nature and approaches to integrate fluorometabolites into the biochemistry of living cells are scarce. In this work, synthetic gene circuits for organofluorine biosynthesis are implemented in the platform bacterium Pseudomonas putida. By harnessing fluoride-responsive riboswitches and the orthogonal T7 RNA polymerase, biochemical reactions needed for in vivo biofluorination are wired to the presence of fluoride (i.e. circumventing the need of feeding expensive additives). Biosynthesis of fluoronucleotides and fluorosugars in engineered P. putida is demonstrated with mineral fluoride both as only fluorine source (i.e. substrate of the pathway) and as inducer of the synthetic circuit. This approach expands the chemical landscape of cell factories by providing alternative biosynthetic strategies towards fluorinated building-blocks.
Calero , P , Volke , D C , Lowe , P , Gotfredsen , C H , O'Hagan , D & Nikel , P I 2020 , ' A fluoride-responsive genetic circuit enables in vivo biofluorination in engineered Pseudomonas putida ' , Nature Communications , vol. 11 , 5045 . https://doi.org/10.1038/s41467-020-18813-x
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DescriptionFunding: This work was supported by grants from The Novo Nordisk Foundation (NNF10CC1016517 and NNF18OC0034818), the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 814418 (SinFonia) and the Danish Council for Independent Research (SWEET, DFF-Research Project 8021-00039B) to P.I.N. We also thank the NMR Center at the Technical University of Denmark and the Villum Foundation for facilitating access to the 600 and 800 MHz NMR spectrometers.
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