Reversible stochastic epigenetic like silencing of the production of pulcherriminic acid in the antimicrobial antagonist Metschnikowia Pulcherrima

The ability to produce pulcherriminic acid is a characteristic feature of yeast species of the pulcherrima clade recently merged under the taxonomic name Metschnikowia pulcherrima. This iron chelator cyclodipeptide forms pulcherrimin, a maroon-red pigment with ferric ions. Its synthesis and secretion into the environment is under the control of closely linked genes referred to as the PUL cluster. The examination of 18 generations of single-cell clones generated from a stock culture of the collection strain 11-1090 (CBS 10359) in this study revealed that the biosynthesis of pulcherriminic acid is reversibly switched on and off during the propagation of cells in a way similar to the epigenetic silencing and activation of gene expression (bimodal active/silent state) in near-heterochromatic regions of other yeast species. As the strain is heterozygous for PUL2 alleles encoding slightly different amino acid sequences and has a plastic genome structure, the efficiency of pulcherriminic acid synthesis in the switched-on state is presumed to depend on which PUL2 allele is active and on structural changes in the genome. The transitions between the active and silent states of pulcherriminic acid synthesis are associated with transitions between the active and silent states of antimicrobial antagonism. This association confirms the primary role of pulcherriminic acid in the antimicrobial antagonism of M. pulcherrima.