Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum

BMC Microbiology

Research Article

Dorit Lubitz¹  Volker F. Wendisch¹ 

[1] Genetics of Prokaryotes, Faculty of Biology and Center for Biotechnology, Bielefeld University, Universitätsstraße 25, 33615, Bielefeld, Germany;

关键词: Corynebacterium glutamicum;    Ciprofloxacin;    DNA gyrase;    Glutamate;    Ornithine;    Putrescine;    Arginine;    Lysine;    2-oxoglutarate;    Overflow metabolism;   

DOI  :  10.1186/s12866-016-0857-6

 received in 2016-05-19, accepted in 2016-10-01,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCorynebacterium glutamicum is a well-studied bacterium which naturally overproduces glutamate when induced by an elicitor. Glutamate production is accompanied by decreased 2-oxoglutatate dehydrogenase activity. Elicitors of glutamate production by C. glutamicum analyzed to molecular detail target the cell envelope.ResultsCiprofloxacin, an inhibitor of bacterial DNA gyrase and topoisomerase IV, was shown to inhibit growth of C. glutamicum wild type with concomitant excretion of glutamate. Enzyme assays showed that 2-oxoglutarate dehydrogenase activity was decreased due to ciprofloxacin addition. Transcriptome analysis revealed that this inhibitor of DNA gyrase increased RNA levels of genes involved in DNA synthesis, repair and modification. Glutamate production triggered by ciprofloxacin led to glutamate titers of up to 37 ± 1 mM and a substrate specific glutamate yield of 0.13 g/g. Even in the absence of the putative glutamate exporter gene yggB, ciprofloxacin effectively triggered glutamate production. When C. glutamicum wild type was cultivated under nitrogen-limiting conditions, 2-oxoglutarate rather than glutamate was produced as consequence of exposure to ciprofloxacin. Recombinant C. glutamicum strains overproducing lysine, arginine, ornithine, and putrescine, respectively, secreted glutamate instead of the desired amino acid when exposed to ciprofloxacin.ConclusionsCiprofloxacin induced DNA synthesis and repair genes, reduced 2-oxoglutarate dehydrogenase activity and elicited glutamate production by C. glutamicum. Production of 2-oxoglutarate could be triggered by ciprofloxacin under nitrogen-limiting conditions.

【 授权许可】

CC BY   
© The Author(s). 2016