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Projekt
Genomic mining for antimicrobial lipopeptides and studies on their biosynthesis
Antragsteller
Professor Dr. Harald Groß
Fachliche Zuordnung
Bioinformatik und Theoretische Biologie
Förderung
Förderung von 2008 bis 2016
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 33421847
The aim of this project is isolate new antimicrobial cyclic lipopeptides (CLPs) and to obtain an indepth understanding of the biosynthesis of the two antibiotics empedopeptin and SB-253514 as a basis for structure optimization. The proline-rich empedopeptin possess significant antibacterial potency and is well tolerated in animal models. The antibacterial lipo-dipeptide SB-253514 represents, despite its unique bicyclic enol-carbamate portion, formally to date the smallest CLP. In the preceding funding period, we identified the mode of action of empedopeptin as well as the genetic locus and the antibacterial activity of SB-253514. However, nothing is known about the biosynthesis of both CLPs and the mode of action of SB-253514. In the case of empedopeptin, we are particularly interested in finding and characterization of the biosynthesis gene cluster and to study the formation of beta-hydroxy-proline moieties since we hypothesize that these side chains enhance interactions with its specific target. Regarding the biosynthesis of SB-253514, we intend to study the intriguing and unprecedented rearrangement process, mediated by a monooxigenase that converts a linear dipeptide precursor into a 5,5-bicyclic enol-carbamate moiety. Furthermore, in collaboration with other groups of the Research Unit the mode of action of SB-253514 will be investigated and congeners of both CLPs will be generated.
DFG-Verfahren
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