title: Forkhead-associated proteins genetically linked to the serine/threonine kinase PknB regulate carbon flux towards antibiotic biosynthesis in Streptomyces coelicolor.
abstract: To date, the function of only two of the 34 predicted serine/threonine protein kinases (STPKs) of Streptomyces coelicolor has been described. Here we report functional analysis of pknB and two linked genes, fhaAB, encoding forkhead-associated (FHA) domain proteins that are part of a highly conserved gene locus in actinobacteria. In contrast to the homologous gene of Mycobacterium tuberculosis, pknB in S. coelicolor is not essential and has no apparent role in defining cell shape. Phosphorylation of recombinant forms of both the full-length protein and N-terminal kinase domain suggest that PknB-mediated signalling in S. coelicolor may be modulated by another factor(s). FhaAB are candidate interacting partners of PknB and loss of their function resulted in deregulation of central carbon metabolism, with carbon flux diverted to synthesis of the antibiotic actinorhodin. The substrate hyphae of the fhaAB mutant also exhibited an unusual cording morphology. The results indicate that inactivation of FHA 'brake' proteins can potentially amplify the function of STPKs and, in this case, provide a means to overproduce antibiotics.
authors.affiliation: Institute of Life Science, Swansea University, Singleton Park, Swansea SA28PP, UK.
authors.forename: Greg
authors.initials: G
authors.lastname: Jones
authors.forename: Ricardo
authors.initials: R
authors.lastname: Del Sol
authors.forename: Ed
authors.initials: E
authors.lastname: Dudley
authors.forename: Paul
authors.initials: P
authors.lastname: Dyson
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D048372:Streptomyces coelicolor / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D051858:Forkhead Transcription Factors; D002244:Carbon; D017346:Protein Serine-Threonine Kinases