Abstract
One key concept in the evolution of new functions is the ability of enzymes to perform promiscuous side-reactions that serve as a source of novelty that may become beneficial under certain conditions. Here, we identify a mechanism where a bacteriophage-encoded enzyme introduces novelty by inducing expression of a promiscuous bacterial enzyme. By screening for bacteriophage DNA that rescued an auxotrophic Escherichia coli mutant carrying a deletion of the ilvA gene, we show that bacteriophage-encoded S-adenosylmethionine (SAM) hydrolases reduce SAM levels. Through this perturbation of bacterial metabolism, expression of the promiscuous bacterial enzyme MetB is increased, which in turn complements the absence of IlvA. These results demonstrate how foreign DNA can increase the metabolic capacity of bacteria, not only by transfer of bona fide new genes, but also by bringing cryptic bacterial functions to light via perturbations of cellular physiology.
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Acknowledgements
Enriched viral DNA from the CF6C, CF7LLP and Por1LT samples were graciously provided by F. L. Rohwer and S. D. Quistad. We acknowledge the assistance of S. Bertilsson in phage purification. The Proteomics Core Facility at the University of Gothenburg is grateful to IngaBritt och Arne Lundbergs Forskningsstiftelse for donating the Orbitrap Fusion Tribrid MS instrument. This work was supported by grants from the Swedish Research Council and the Knut and Alice Wallenberg foundation (to M.S. and D.I.A.).
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J.J.H, O.W., A.S., M.S. and D.I.A. designed the experiments. J.J.H., O.W., M.K., A.S. and M.S. carried out the experiments. U.E. analysed activity data. J.J.H, O.W., M.S. and D.I.A. wrote the manuscript with input from all authors. E.V. carried out the proteomic analysis.
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Supplementary Information
Supplementary Figures 1–8; Legends for Supplementary Tables 1–4; Supplementary References
Dataset 1
Supplementary Table 1: Data and lists of hits in screen
Dataset 2
Supplementary Table 2: HHpred searches with inserts sequences directing ΔilvA prototrophy
Dataset 3
Supplementary Table 3: Hierarchical clustering of TMT and RNA-seq data
Dataset 4
Supplementary Table 4: Strains and primers list
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Jerlström Hultqvist, J., Warsi, O., Söderholm, A. et al. A bacteriophage enzyme induces bacterial metabolic perturbation that confers a novel promiscuous function. Nat Ecol Evol 2, 1321–1330 (2018). https://doi.org/10.1038/s41559-018-0568-5
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DOI: https://doi.org/10.1038/s41559-018-0568-5