Optimization of a fed-batch fermentation process for production of bleomycin by Streptomyces mobaraensis ATCC 15003

Abstract

The objective of this work was to optimize inoculum size and pH for rapid production of bleomycin by Streptomyces mobaraensis ATCC 15003 by fed-batch fermentation. In both batch- and fed-batch fermentations, neither production period for bleomycin by S. mobaraensis nor the amount of BLM were affected by increasing the inoculum size from regular 10 to 30% (v/v) level. A fed-batch bioreactor not only shortened the lag phase of BLM production from 114 to 60 h, but also fed-batch fermentation
enhanced BLM production when combined with an appropriate pH profile with no effect on the amount produced. Due to the substrate inhibition that takes place at high levels of carbon source, fed-batch fermentation was proposed as a better alternative for BLM production. The combined effects of batch and fed-batch fermentation and various pH profiles on BLM production in a bioreactor were evaluated. The tested pH profiles included; (1) a constant pH profile at 6.8 (profile1); (2) a constant pH profile with
a period of auto-acidification for 72 h (profile2) and (3) a step-wise pH profile with pH adjustment every 24 h (profile3). When profile 3 was applied, fed-batch fermentation enhanced BLM production in the bioreactor and yielded about two-fold higher BLM concentration than the irrespective batch fermentation. On the other hand, constant pH profile or that which included one period of autoacidification (profiles 1 and 2) resulted in an insignificantly difference BLM production in fed-batch fermentation. Overall, this study suggested that fed-batch fermentation can be successfully used to enhance BLM production in bioreactor especially with fluctuated pH-profile.

Key words: Bleomycin, Streptomyces mobaraensis, rapid production, fed-batch fermentation.