TY  - THES
T1  - Studies on the biosynthesis of complex natural products from myxobacteria
A1  - Buntin,Kathrin
Y1  - 2010/06/09
N2  - Many myxobacterial natural products display unusual structural features and/or a novel bioactivity, making these secondary metabolites attractive targets for study. This thesis describes the elucidation of the biosynthetic pathways to the ajudazols and thuggacins in Chondromyces crocatus Cm c5 and the thuggacins in Sorangium cellulosum So ce895. Using experiments in vitro and in vivo, we have shown that the thioesterase (TE) domain of the ajudazol assembly line "chaperones'; the formation of the characteristic isochromanone ring, thus placing it within a novel class of TE enzymes. In addition, we have demonstrated the involvement of two P450 enzymes in post-assembly line modification of ajudazol. 
Distinct variants of the anti-tuberculosis macrolide thuggacins are produced by C. crocatus and S.cellulosum. The basis for this architectural diversity has been elucidated by identifying the biosynthetic pathways in both myxobacteria, and comparing them in detail. In the course of this analysis, a crotonyl-CoA reductase/carboxylase homologue was discovered in the S. cellulosum thuggacin gene cluster, and was shown to participate in the assembly of an unusual hexyl side chain. Moreover, evidence was provided that the distinct pattern of hydroxylation observed in the C. crocatus and S. cellulosum thuggacins may results from variable action of a conserved FMN-dependent monooxygenase. 
Finally, we report experiments to probe the formation of the pyrrole starter unit in leupyrrin biosynthesis in Sorangium cellulosum So ce690, and the biochemical investigation of the mechanism by which the disorazol dilactone structure is generated in Sorangium cellulosum So ce12. 

KW  - Biosynthese
KW  - Myxobakterien
KW  - Polyketid-Synthasen
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2010/3152
ER  -