Enhancer Binding Proteins Act as Hetero-oligomers and Link Secondary Metabolite Production to Myxococcal Development, Motility, and Predation

SummaryMotile predatory Myxobacteria are producers of multiple secondary metabolites and, on starvation, undergo concerted cellular differentiation to form multicellular fruiting bodies. These abilities demand myxobacterial genomes to encode sophisticated regulatory networks that are not satisfactorily understood. Here, we present two bacterial enhancer binding proteins (bEBPs) encoded in Myxococcus xanthus acting as direct regulators of secondary metabolites intriguingly exhibiting activating and inhibitory effects. Elucidation of a regulon for each bEBP enabled us to unravel their role in myxococcal development, predation, and motility. Interestingly, both bEBPs are able to interact by forming a hetero-oligomeric complex. Our findings represent an alternative mode of operation of bEBPs, which are currently thought to enhance promoter activity by acting as homo-oligomers. Furthermore, a direct link between secondary metabolite gene expression and predation, motility, and cellular development could be shown for the first time.

Graphical AbstractFigure optionsDownload high-quality image (223 K)Download as PowerPoint slideHighlights
► The bEBPs HsfA and MXAN4899 are direct regulators exhibiting activating and inhibiting effects on transcription
► HsfA and MXAN4899 exhibit a mode of operation: hetero-oligomerization
► The bEBPs link secondary metabolite production to development, motility, and predation
► The results open ways of interpretation in elucidation of complex regulatory networks