title: Continuous enhancement of iturin A production by Bacillus subtilis with a stepwise two-stage glucose feeding strategy.
abstract: 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.
authors.affiliation: Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan, 430062, China. goldtiger1980@163.com.
authors.forename: Hu
authors.initials: H
authors.lastname: Jin
authors.affiliation: Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan, 430062, China. likunpeng123654@126.com.
authors.forename: Kunpeng
authors.initials: K
authors.lastname: Li
authors.affiliation: Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan, 430062, China. niuyanxing@caas.cn.
authors.forename: Yanxing
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan, 430062, China. whguomian@163.com.
authors.forename: Mian
authors.initials: M
authors.lastname: Guo
authors.affiliation: Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan, 430062, China. cjhu@oilcrops.cn.
authors.forename: Chuanjiong
authors.initials: C
authors.lastname: Hu
authors.affiliation: Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan, 430062, China. chenshouwen@mail.hzau.edu.cn.
authors.forename: Shouwen
authors.initials: S
authors.lastname: Chen
authors.affiliation: Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan, 430062, China. jiagongzx@oilcrops.cn.|Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan, 430062, China. jiagongzx@oilcrops.cn.
authors.forename: Fenghong
authors.initials: F
authors.lastname: Huang
mesh_terms: D001412:Bacillus subtilis / Q000378:metabolism*; D061249:Batch Cell Culture Techniques; D061046:Biological Control Agents / Q000378:metabolism; D019149:Bioreactors / Q000382:microbiology; D029741:Brassica rapa / Q000378:metabolism*; D005285:Fermentation; D005947:Glucose / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D010456:Peptides, Cyclic / Q000096:biosynthesis*
chemical_list: D061046:Biological Control Agents; D010456:Peptides, Cyclic; C013579:iturin A; D005947:Glucose; D009584:Nitrogen