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Title: A conserved gram-positive signalling gene cluster : phylogeny and function
Author: Jones, Greg
Awarding Body: Swansea University
Current Institution: Swansea University
Date of Award: 2008
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All sequenced actinobacteria to date contain a conserved gene cluster found close to the origin of replication of the chromosome. This gene cluster contains a number of genes devoted to both signalling on serine and threonine residues a serine/threonine protein kinase (STPK), two ‘forkhead associated’(FHA) domains, and a ser/thr phosphatase as well as genes devoted to cell wall synthesis. Bioinformatic analysis reveals variations of the cluster conserved in firmicute genomes, implying a conservation of function. The key gene in this cluster is the STPK, as it is a transmembrane protein whose extracellular portion consists of four ‘PASTA’ domains which seem likely to be sensing peptidoglycan monomers associated with cell elongation. Mutation of the genes associated with signalling in Streptomyces coelicolor causes the early onset of secondary metabolism and aerial development, implying a link between the state of the cell wall and the control of metabolic flux. The supplementation of growth media with metabolic intermediates reveals a more direct link between FHA domains and metabolic flux, with excess citrate causing a particular increase in secondary metabolism. Further proteomic analysis confirms the involvement of proteins dedicated to metabolic functions, including the exclusive presence of phosphorylated citrate synthase in the FHA domain mutants. The emerging picture is one of a pleiotropic network of proteins, using serine / threonine phosphorylation as a signalling device, controlling metabolic flux in response to a variety of environmental signals.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available