Pristinamycin / PTT Biosynthesis
AG PD Dr. Yvonne Mast
The main focus of our research group is the investigation of regulatory mechanisms in antibiotic-producing streptomycetes. Hereby, we are especially interested in regulation processes associated with two natural compounds: phosphinothricin-tripeptide (PTT) and pristinamycin.
The PTT biosynthesis serves as a model for the analysis of the evolution of secondary metabolite biosynthesis. Three enzymes which are directly derived from enzymes of the TCC cycle are involved in the biosynthesis of a precursor of PTT. By mutagenesis experiments and enzyme assays, we are studying the evolution of the proteins to biochemically different enzymes. Furthermore, the PTT biosynthesis seems to be an archetype of the non-ribosomal peptide synthesis.
Pristinamycin is a mixture of two types of chemically unrelated compounds: pristinamycin PI and PII. PI and PII have a synergistic effect and show bactericidal activity against many Gram-positive bacteria and some Gram-negatives. We showed that the genes responsible for pristinamycin biosynthesis are not organized as a single cluster but spread over 210 kb together with a further type II PKS gene cluster. This makes the pristinamycin gene region the largest antibiotic ‘supercluster’ that is known so far. At the moment, we functionally characterize this ’gene region’ by knock-out mutagenesis and investigate the pristinamycin biosynthesis. One of our projects here is the investigation a novel pathway of L-phenylglycine biosynthesis, which is a component of PI. In addition, we are studying the regulation of pristinamycin biosynthesis.
Current research topics
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- Model for the evolution of secondary metabolite biosynthesis
- Regulatory function of S. viridochromogenes aconitase
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- Cryptic pristinaespiralis polyketide
- Regulation of pristinamycin biosynthesis
- Phenylglycin biosynthesis
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- Exploiting underexplored translation inhibitors
- Isolation of new unique natural compounds
- Generation of novel and resistance-breaking agents
Our research is funded by