Sunday, July 24, 2011
Grand Ballroom, 5th fl (Sheraton New Orleans)
Recent studies have shown that the economically important phytopathogen Ralstonia solanacearum produces secondary metabolites under the control of plant-induced virulence regulators (1, 2), assuming a role of these compounds in host adaptation and/or pathogenesis. Comparative genomics has now led to the discovery of an orphan polyketide synthase/ nonribosomal peptide synthetase (PKS/NRPS) gene cluster, which is conserved among different phylotypes of the Ralstonia solanacearum species complex. The domain architecture of the PKS/NRPS biosynthesis enzymes suggested the locus to encode the production of a yersiniabactin-like siderophore. Targeted gene inactivation and metabolic profiling confirmed the locus to be operational under iron deficient conditions and guided the isolation of the antibiotic micacocidin, which was previously reported from Pseudomonas sp. (3). Exploiting the rather unspecific affinity of micacocidin towards different metal ligands, we investigated the cellular uptake and thus the siderophore properties of this natural product after complexation of the radioactive gallium isotope 68Ga.
Micacocidin and yersiniabactin represent a textbook example of how minor deviations between biosynthetic assembly lines may translate into chemical diversity. This study will facilitate future bioinformatic predictions on secondary metabolites from related pathways, which are increasingly detected in whole genome sequencing projects.
1. Delaspre et al., Proc. Natl. Acad. Sci. USA, 104, 15870-15875 (2007)
2. Schneider et al., ChemBioChem, 10, 2730-2732 (2009)
3. Kobayashi et al., J. Antibiot., 51, 328-332 (1998)