Didehydroroflamycoin pentaene macrolide family from Streptomyces durmitorensis MS405T: production optimization and antimicrobial activity
Article first published online: 2 SEP 2013
© 2013 The Society for Applied Microbiology
Journal of Applied Microbiology
Volume 115, Issue 6, pages 1297–1306, December 2013
How to Cite
Stankovic, N., Senerovic, L., Bojic-Trbojevic, Z., Vuckovic, I., Vicovac, L., Vasiljevic, B. and Nikodinovic-Runic, J. (2013), Didehydroroflamycoin pentaene macrolide family from Streptomyces durmitorensis MS405T: production optimization and antimicrobial activity. Journal of Applied Microbiology, 115: 1297–1306. doi: 10.1111/jam.12326
- Issue published online: 15 NOV 2013
- Article first published online: 2 SEP 2013
- Accepted manuscript online: 13 AUG 2013 08:11AM EST
- Manuscript Revised: 6 AUG 2013
- Manuscript Accepted: 6 AUG 2013
- Manuscript Received: 18 APR 2013
- Ministry of Science and Technological Development of the Republic of Serbia. Grant Numbers: 173048 and 173004, MSTD, 2011-2014
The aim of this study was to improve production of pentaene 32,33-didehydroroflamycoin (DDHR) in Streptomyces durmitorensis MS405 strain to obtain quantities sufficient for in depth analysis of antimicrobial properties.
Methods and Results
Through classical medium optimization conditions for stable growth, DDHR production within 7 days of incubation was established. Yields of 215 mg l−1 were achieved in shake flask experiments in complex medium with mannitol as the primary carbon source. DDHR had poor antibacterial activity with minimal inhibitory concentrations (MIC) of 400 μg ml−1 for Staphylococcus aureus and Bacillus subtilis, while MIC of 70 μg ml−1 was determined for Candida albicans. Using flow cytometry and fluorescent microscopy, it was demonstrated that DDHR induced membrane damage in C. albicans followed by cell death. Combination studies with known antifungal nystatin showed that DDHR is a promising agent for the development of novel antimycotic treatments potentially less toxic for human cells.
Pentaene didehydroroflamycoin has no antibacterial activity but can be further developed for the application in antifungal therapy.
Significance and Impact of the Study
This study is the first report on the stable and production in high yields of a novel pentaene family that acts on Candida cell membranes and can be used in combination with known antifungals. Polyenes are still antifungal antibiotics of choice, and therefore, isolation and production of new lead structures are highly significant.