A bacteriophage enzyme induces bacterial metabolic perturbation that confers a novel promiscuous function.. Escherichia coli str. K-12 substr. MG1655

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 E. coli mutant carrying a deletion of the ilvA gene, we show that bacteriophage-encoded S-adenosylmethionine (SAM) hydrolases reduce SAM levels. Via 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. Overall design: RNA-seq profiles of two plasmid constructs, inducible by IPTG, selected as providing metabolic rescue to E. coli ilvA-. The experiment was performed in duplicates with and without IPTG induction for the insert-bearing plasmids. A duplicate control experiment with empty plasmid in the same E. coli strain (with IPTG added) was also performed. Samples from the same experiments were processed both for RNA-seq and 10-plex TMT quantitative shot-gun proteomics. The TMT dataset is available at ProteomeXchange with identifier PXD005236.