TP8
Hormaomycin is a nonribosomal peptide antibiotic isolated from Streptomyces griseoflavus W-384. It contains a number of unprecedented nonproteinogenic building blocks bearing chlorine, nitro or cyclopropyl moieties.
In Streptomyces spp., hormaomycin acts as bacterial hormone by inducing cellular morphogenesis and increasing production titers of antibiotics. In addition, hormaomycin is an antibiotic itself with high potency and selectivity against various coryneform actinomycetes.
In feeding experiments amino acid analogs were readily incorporated, resulting in the production of numerous modified hormaomycins, among which hormaomycin D2 exhibits novel antifungal activity. This suggests that the biosynthetic machinery is unusually flexible and that this property could be exploited to generate improved antibiotics or to obtain elicitors to increase fermentation yields in antibiotic production. In the current project hormaomycin biosynthesis will be studied at the genetic and enzymatic level to address these issues.
Furthermore, in collaboration with other groups of the Research Unit the mode of action for the antibacterial and the possibly interlinked hormonal activity will be investigated, and the antibiotic-inducing properties will be studied with additional bacterial taxa that are important natural product sources.
