Forkhead-associated proteins genetically linked to the serine/threonine kinase PknB regulate carbon flux towards antibiotic biosynthesis in Streptomyces coelicolor.
Bottom Line: 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.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 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.
Affiliation: Institute of Life Science, Swansea University, Singleton Park, Swansea SA28PP, UK.Show MeSH
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Mentions: Increased production of actinorhodin by the pknB mutant was quantified during growth in submerged culture. The mutant produced approximately four times the yield of the parental strain (Fig. 2), but the overall growth rate was unaffected. We have previously observed that addition of osmolyte stimulates production of actinorhodin by the parental strain M145 (Bishop et al., 2004). However, in contrast, actinorhodin production by the pknB mutant was partly suppressed by addition of osmolyte (Fig. 2).
Affiliation: Institute of Life Science, Swansea University, Singleton Park, Swansea SA28PP, UK.