| |
| author |
Ryann Callaghan
| | title |
Production of Kibdelomycin by Kibdelosporangium sp. and Discovery of Potential Structural Analogues
| | abstract |
Kibdelomycin is a natural product produced by the actinomycete
Kibdelosporangium sp., and was discovered by Merck & Co. in the late-2000s (Phillips et
al. 2011). It is a type II topoisomerase inhibitor with antibiotic activity against Gram-positive bacteria.
In this study, fermentation conditions were established for
Kibdelosporangium sp. to improve kibdelomycin production, with galactose currently the
best carbon source in a complex medium. To further improve production of kibdelomycin
for future chemical modification studies, we have successfully implemented a strain
improvement procedure involving the selection of production strains resistant to
aminoglycosides such as streptomycin and gentamicin. The generation of cumulative
antibiotic resistance has previously worked for other actinomycete bacteria, and is
correlated to ribosomal mutations that cause overproduction of natural products (Hu and
Ochi 2001; Wang et al. 2008; Tanaka et al. 2013). Utilizing this method in
Kibdelosporangium sp. resulted in improved strains which produce up to 50.4% more
kibdelomycin. LC-MS analysis of fermentation extracts revealed production of
kibdelomycin and five potential structural analogues as well as a kibdelomycin isomer.
These analogues share characteristic UV profiles of kibdelomycin but differ in retention
time and molecular weight as well as mass spectrometry fragmentation patterns. Overall,
media development and strain improvement were important steps taken for the future
development of kibdelomycin, and identification of structural analogues may assist in
finding a compound with maximum antibiotic activity and minimum serum antagonism.
| | school |
The College of Liberal Arts, Drew University
| | degree |
B.A. (2019)
|
| advisor |
Neal Connors
|
| committee |
Joanna Miller
Adam Cassano
|
| full text | RCCallaghan.pdf |
| |
