In our efforts in lasso peptide genome mining, we have found two lasso peptide gene clusters that contain genes encoding a toxin-antitoxin (TA) module. In one case, the TA module was the well-characterized HipAB pair, but the other TA module was characterized only from genetic and bioinformatic perspectives. We have carried out bioinformatic studies that suggest that this TA module is exceptionally widespread, appearing in over 2000 different bacterial strains. We have heterologously expressed this novel TA module in <i>E. coli</i> and confirmed that the toxin causes a growth arrest phenotype to which the antitoxin can serve as an antidote. Mutagenesis of the toxin at conserved residues led to identification of residues key for the toxic phenotype. Since the mechanism of the toxin remained unclear, we solved the crystal structure of the toxin in complex with a fragment of the antitoxin. This talk will discuss this structure as well as the cellular targets and function of the toxin.

A novel widespread toxin-antitoxin module

255th National Meeting (2018)

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