Project Area B

Cellular Mechanisms

Antibiotic biosynthesis in producer cells

Projects included in Project Area B aim at increasing our understanding of the antibiotic biosynthesis process. A central aspect is the location and composition of the biosynthetic complex in the course of the growth and production phases of the producer cell culture as well as the corresponding interactions between components of the biosynthetic machinery. We intend to explore regulation of antibiotic biosynthesis not only on the level of gene expression but also on the level of posttranslational regulation in natural producer cells. Connections between primary and secondary metabolism supporting precursor supply will be investigated and reasons for unusual natural product modifications will be examined. In addition, we will explore the impact of antibiotic production on the physiology of the producer cell, studying adaptations, benefits, and burden in order to better understand gene cluster spread and evolution.

Project B01

Spatial and temporal cellular assembly of the glycopeptide biosynthetic complex

Balhimycin, a glycopeptide synthesized by Amycolatopsis balhimycina, is a heptapeptide, which is modified by cyclization, methylation, halogenation, and glycosylation. Using genetics and biochemistry, its biosynthetic steps have been elucidated indicating the occurrence of a large multi-enzyme complex that catalyzes amino acid assembly as well as various modifications. Whereas the chronology of the reactions could be defined, nothing is known about the positioning and dynamics of such a super-complex. Protein interaction studies and state-of-the-art microscopy will localize the complexes in the cell, identify further putative interaction partners, and define the temporal assembly of the complex.

Principal Investigator
Prof. Dr. Wolfgang Wohlleben
Interfakultäres Institut für Mikrobiologie und Infektionsmedizin
Mikrobielle Wirkstoffe / Biotechnologie
Eberhard Karls Universität Tübingen
Auf der Morgenstelle 28, 72076 Tübingen
+49 (0)7071 29-76944
wolfgang.wohllebenbiotech.uni-tuebingen.de
PD Dr. Efthimia Stegmann
Interfakultäres Institut für Mikrobiologie und Infektionsmedizin
Mikrobielle Wirkstoffe / Biotechnologie
Eberhard Karls Universität Tübingen
Auf der Morgenstelle 28, 72076 Tübingen
+49 (0)7071 29-78840
evi.stegmannbiotech.uni-tuebingen.de