Heterogeneous regulation of bacterial natural product biosynthesis via a novel transcription factor

Abstract

Biological diversity arises among genetically equal subpopulations in the same environment, a phenomenon called phenotypic heterogeneity. The life cycle of the enteric bacterium <i>Photorhabdus luminescens</i> involves a symbiotic interaction with nematodes as well as a pathogenic association with insect larvae. <i>P. luminescens</i> exists in two distinct phenotypic forms designated as primary (1°) and secondary (2°). In contrast to 1° cells, 2° cells are non-pigmented due to the absence of natural compounds, especially anthraquinones (AQs). We identified a novel type of transcriptional regulator, AntJ, which activates expression of the <i>antA</i>-<i>I</i> operon responsible for AQ production. AntJ heterogeneously activates the AQ production in single <i>P. luminescens</i> 1° cells, and blocks AQ production in 2° cells. AntJ contains a proposed ligand-binding WYL-domain, which is widespread among bacteria. AntJ is one of the rare examples of regulators that mediate heterogeneous gene expression by altering activity rather than copy number in single cells.