TY  - THES
T1  - Natural product biosynthesis in myxobacteria : studies on enzymatic versatility and secondary metabolite diversity
A1  - Krug,Daniel
Y1  - 2009/06/18
N2  - In this work, the biosynthesis of secondary metabolites in myxobacteria was investigated, with particular focus on the functional and biochemical characterization of enzymes furnishing biosynthetic pathways with unusual building blocks. A novel member of the tyrosine aminomutase (TAM) enzyme family, CmdF, was shown to supply (R)-beta-tyrosine for incorporation into the chondramides by Chondromyces crocatus. Site-directed mutagenesis demonstrated the feasibility of modulating the stereoselectivity exhibited by CmdF through genetic engineering. The cloning and characterization of additional TAMs revealed a high degree of evolutionary diversification within the emerging TAM enzyme family. Furthermore, the structural elucidation and biosynthesis of newly discovered metabolites from Stigmatella aurantiaca, the imidacins, is reported. These compounds consist of a fatty-acid like scaffold, but additionally feature an unique imidazole acryl moiety and a rare cyclopropane ring. Imidacin formation depends on the supply of an unprecedented urocanic acid precursor by a histidine ammonia lyase (HAL), revealing for the first time the involvement of HAL in bacterial secondary metabolism.
In addition, a metabolomics-based approach for the mining of myxobacterial metabolite profiles was devised. High-resolution mass spectrometry, combined with statistical interpretation by principal component analysis (PCA), was employed to highlight compounds which constitute significant differences in a set of highly complex samples. This technique uncovered a strikingly high level of intraspecific diversity in the secondary metabolome of Myxococcus xanthus.
KW  - Naturstoff
KW  - Sekundärmetabolit
KW  - Myxobakterien
KW  - Biosynthese
KW  - Vielfalt
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2009/2192
ER  -