The diazeniumdiolate signal valdiazen is a global regulator of virulence and secondary metabolism in Burkholderia plantarii

Here, we show that the ham gene cluster directs the biosynthesis of the diazeniumdiolate signal valdiazen and is required for both antifungal activity and virulence. Transcriptome analysis identified a valdiazen regulon comprising 390 genes, including genes within and flanking the ham cluster, indicating roles in signal modulation, transport and autoregulation.

Valdiazen also globally controls genes involved in secondary metabolism and the expression of several bioactive metabolites, including those required for tropolone biosynthesis and the type III secretion system. We further identify tropolone as the major antifungal metabolite of B. plantarii and demonstrate that its antifungal activity is mediated through iron chelation. An AraC family transcriptional regulator located upstream of the ham cluster regulates valdiazen biosynthesis and the downstream regulatory network.