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Background  The production of secondary metabolites with antibiotic properties is a common characteristic to entomopathogenic bacteria  Xenorhabdus  spp. These metabolites not only have diverse chemical structures but also have a wide range of bioactivities with medicinal and agricultural interests such as antibiotic, antimycotic and insecticidal, nematicidal and antiulcer, antineoplastic and antiviral. It has been known that cultivation parameters are critical to the secondary metabolites produced by microorganisms. Even small changes in the culture medium may not only impact the quantity of certain compounds but also the general metabolic profile of microorganisms. Manipulating nutritional or environmental factors can promote the biosynthesis of secondary metabolites and thus facilitate the discovery of new natural products. This work was conducted to evaluate the influence of nutrition on the antibiotic production of  X. bovienii  YL002 and to optimize the medium to maximize its antibiotic production.    Results  Nutrition has high influence on the antibiotic production of  X. bovienii  YL002. Glycerol and soytone were identified as the best carbon and nitrogen sources that significantly affected the antibiotic production using one-factor-at-a-time approach. Response surface methodology (RSM) was applied to optimize the medium constituents (glycerol, soytone and minerals) for the antibiotic production of  X. bovienii  YL002. Higher antibiotic activity (337.5 U/mL) was obtained after optimization. The optimal levels of medium components were (g/L): glycerol 6.90, soytone 25.17, MgSO 4 ·7H 2 O 1.57, (NH 4 ) 2 SO 4  2.55, KH 2 PO 4  0.87, K 2 HPO 4  1.11 and Na 2 SO 4  1.81. An overall of 37.8% increase in the antibiotic activity of  X. bovienii  YL002 was obtained compared with that of the original medium.    Conclusions  To the best of our knowledge, there are no reports on antibiotic production of  X. boviebii  by medium optimization using RSM. The results strongly support the use of RSM for medium optimization. The optimized medium not only resulted in a 37.8% increase of antibiotic activity, but also reduced the numbers of experiments. The chosen method of medium optimization was efficient, simple and less time consuming. This work will be useful for the development of  X. bovienii  cultivation process for efficient antibiotic production on a large scale, and for the development of more advanced control strategies on plant diseases.

Improvement of antibiotic activity of Xenorhabdus bovienii by medium optimization using response surface methodology