TY  - THES
T1  - Deciphering novel mechanisms of bacterial secondary metabolite biosynthetic pathways
A1  - Pistorius,Dominik
Y1  - 2011/10/31
N2  - Bacterial secondary metabolites display enormous structural diversity with astonishing biological activities. This thesis confers new insights into the biosynthesis of the myxobacterial secondary metabolites tubulysins by both in vitro and in vivo experiments, along with the identification and characterization of new structural variants.
The cryptic biosynthetic pathway of the aurachins in Stigmatella aurantiaca Sg a15 was elucidated. In vitro experiments revealed an unparalleled priming mechanism for the anthranilate starter unit. In vivo gene inactivation experiments resulted in the identification of the tailoring functionalities responsible for the successive transformations from aurachin D to aurachin A.
Another topic of this thesis was the investigation of the biosynthesis of 2-heptyl-4(1H)-quinolone (HHQ), an important quorum sensing molecule in Pseudomonas aeruginosa. In vitro reconstitution of HHQ biosynthesis by employing recombinant PqsD protein has shed light on this enzyme and its substrates, leading to the development of an in vitro test system for the identification of HHQ biosynthesis inhibitors, a promising alternative target in P. aeruginosa therapy. 
Exploiting the newly sequenced genome of S. aurantiaca Sg a15 a genome mining approach, combining targeted gene inactivation with a statistics based comparative secondary metabolite profile analysis, was adapted and employed. This culminated in the identification and characterization of the rhizopodin biosynthetic gene cluster.
KW  - Biosynthese
KW  - Polyketid-Synthasen
KW  - Antibiotikum
KW  - Sekundärmetabolit
KW  - Pseudomonas aeruginosa
KW  - Stigmatella aurantiaca
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2011/4408
ER  -