B5: Immunity mechanism of ADEP producer Streptomyces hawaiiensis NRRL 15010

Group Leader

Prof. Dr. Heike Brötz-Oesterhelt
Interfaculty Institute of Microbiology and Infection Medicine (IMIT)
Department of Microbial Bioactive Compounds
Eberhard-Karls-Universität Tübingen
Auf der Morgenstelle 28
72076 Tübingen
Phone: +49-7071 29-74105
Fax: +49-7071 29-5094
Email: heike.broetz-oesterhelt(at)uni-tuebingen.de

PhD Student

Laura Reinhardt
Phone: +49-7071 29-74726
email: laura.reinhardt(at)uni-tuebingen.de

Summary

Streptomyces hawaiiensis NRRL 15010 is the producer of an antibacterial complex A54556, precursor of a new class of acyldepsipeptide antibiotics.
Target of ADEP is ClpP, the proteolytic core of the bacterial caseinolytic protease. In the natural context ClpP is controlled by Clp-ATPases to only degrade defective proteins and particular regulatory proteins. By binding to docking positions at ClpP that are normally occupied by the Clp-ATPases, ADEPs activates ClpP for non-specific protein degradation that is detrimental to the cell. At the same time, by blocking ClpP / Clp-ATPase interaction, all natural functions of the Clp protease system in protein homeostasis and regulatory proteolysis are prevented.
In contrast to most bacteria, which contain only one ClpP gene, Streptomycetes have several ClpP isoforms and ClpP function is essential for growth under all conditions. In this study, we investigate how the producer strain S.hawaiiensis survives the production of ADEP.