Optimized Production of the Allylamine Antifungal "Terbinafine" by Lysinibacillus Isolate MK212927 Using Response Surface Methodology

Purpose: We aimed to optimize the factors affecting the production of the allylamine antifungal, terbinafine, by Lysinibacillus isolate MK212927, a natural producer of this broad-spectrum fungicidal compound. Methods: We employed a central composite design to optimize the five most important variables influencing the production of terbinafine which were carbon source, nitrogen source, temperature, pH and agitation. Results: The optimum conditions were found to be starch 5 g/L, ammonium chloride 5 g/L, temperature 32 degrees C, agitation 150 rpm and pH 7. The actual response (inhibition zone diameter) was highly comparable to the value predicted by the model, indicating a valid model. Using the standard calibration curve of terbinafine, the optimized conditions resulted in an increase in the antifungal metabolite production (terbinafine) by about 1.6-fold (1814.662 mu g/mL compared to 1165.550 mu g/mL under standardized conditions). Conclusion: This is the first report, to the best of our knowledge, on optimized production of terbinafine by Lysinibacillus species. Hence, these findings may be useful as baseline data for scaling up the production of terbinafine from a natural microbial source.