A new family of aspartyl phosphate phosphatases targeting the sporulation transcription factor Spo0A of Bacillus subtilis

The initiation of the sporulation developmental pathway in Bacillus subtili s is controlled by the phosphorelay, a multicomponent signal transduction s ystem. Multiple positive and negative signals are integrated by the phospho relay through the opposing activities of histidine protein kinases; and asp artyl phosphate phosphatases. Three members of the Rap family of phosphatas es (RapA, RapB and RapE) specifically dephosphorylate the SpoOF similar toP response regulator intermediate, while the SpoOA similar toP transcription factor is specifically dephosphorylated by the SpoOE phosphatase and, as s hown here, the newly identified YnzD and Yisl proteins. The products of the YnzD and Yisl genes are highly homologous to SpoOE and define a new family of phosphatases with a distinct signature motif in their amino acid sequen ce. As negative regulators of the developmental pathway, YnzD and Yisl inhi bit spore formation if overexpressed, while a chromosomal deletion of their coding sequences results in increased sporulation frequency. Transcription of the ynzD, yisl and spoOE genes is differentially regulated and generall y induced by growth conditions antithetical to sporulation. Negative signal s interpreted by aspartyl phosphate phosphatases appear to be a common mech anism in Gram-positive spore-forming microorganisms.