Continuous enhancement of iturin A production by Bacillus subtilis with a stepwise two-stage glucose feeding strategy

Background: The lipopeptide antibiotic iturin A is an attractive biopesticide with the potential to replace chemical-based pesticides for controlling plant pathogens. However, its industrial fermentation has not been realized due to the high production costs and low product concentrations. This study aims to enhance iturin A production by performing a novel fermentation process with effective glucose feeding control using rapeseed meal as a low-cost nitrogen source. Results: We demonstrated that continuous and significant enhancement of iturin A production could be achieved by a novel two-stage glucose-feeding strategy with a stepwise decrease in feeding rate. Using this strategy, the ratio of spores to total cells could be maintained at a desirable/stable level of 0.80-0.86, and the reducing sugar concentration could be controlled at a low level of 2-3 g/L so that optimal substrate balance could be maintained throughout the feeding phase. As a result, the maximum iturin A concentration reached 1.12 g/L, which was two-fold higher than that of batch culture. Conclusions: This is the first report which uses control of the glucose supply to improve iturin A production by fed-batch fermentation and identifies some important factors necessary to realize industrial iturin A production. This approach may also enhance the production of other useful secondary metabolites by Bacillus subtilis.