TY  - THES
T1  - Biosynthesis and regulation of production of the antibiotic Myxovirescin A in Myxococcus xanthus DK1622
T3  - ChemBioChem. -  DOI: 10.1002/cbic.200600075 ; DOI: 10.1002/cbic.200700017 ; DOI: 10.1002/cbic.200700153
A1  - Simunovic,Vesna
Y1  - 2007/07/06
N2  - Myxobacteria produce a variety of secondary metabolites displaying important biological activities. Recent sequencing of the Myxococcus xanthus DK1622 genome revealed its high potential for the production of secondary metabolites and led to the identification of the myxovirescin biosynthetic gene cluster. In silico analysis of myxovirescin megasynthetase resulted in the proposal that a number of discrete enzymes work together with the multimodular PKS to build myxovirescin scaffold, unique for the presence of two different beta-alkyl groups. To test the myxovirescin biosynthetic model, fourteen in-frame deletion mutants in the myxovirescin biosynthetic gene cluster were created, and their effects on the production of myxovirescin antibiotics evaluated by HPLC-MS analysis of the resulting mutant extracts. Novel myxovirescin analogues arising from certain mutant backgrounds were structurally elucidated to identify the specific positions of these modifications. In silico analysis of an additional 11 kb region encoded upstream from the myxovirescin gene clusters were proposed to be involved in the regulation of its production. Genetic disruption of a gene encoding for a serine/threonine kinase, and two additional genes encoding for proteins of unknown functions, were shown to positively regulate myxovirescin production.
KW  - Myxovirescine
KW  - Myxococcus xanthus
KW  - Biosynthese
KW  - Antibiotikum
KW  - Polyketide
KW  - Sekundärmetabolit
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2007/1186
ER  -