Abstract
BACKGROUND: Microorganisms are a rich source of structurally diverse secondary metabolites that exert a major impact on the control of infectious diseases and other medical conditions. The biosynthesis of these metabolites can be improved by manipulating the nutritional or environmental factors. This work evaluates the effects of fermentation parameters on the production of a lactone compound effective against Candida albicans by Penicillium verruculosum MKH7 under submerged fermentation. Design-Expert version8.0 software was used for construction of the experimental design and statistical analysis of the experimental data. RESULTS: The important factors influencing antibiotic production selected in accordance with the Plackett-Burman design were found to be initial pH, temperature, peptone, MgSO(4).7H(2)O. Orthogonal central composite design and response surface methodology were adopted to further investigate the mutual interaction between the variables and identify the optimum values that catalyse maximum metabolite production. The determination coefficient (R(2)) of the fitted second order model was 0.9852. The validation experiments using optimized conditions of initial pH 7.4, temperature 27 °C, peptone 9.2 g/l and MgSO(4).7H(2)O 0.39 g/l resulted in a significant increase (almost 7 fold from 30 to 205.5 mg/l) in the metabolite production which was in agreement with the prediction (211.24 mg/l). Stability of the compound was also assessed on the basis of its response to physical and chemical stresses. CONCLUSIONS: So far as our knowledge goes, till date there are no reports available on the production of antibiotics by Penicillium verruculosum through media optimization using RSM. Optimization not only led to a 7 fold increase in metabolite yield but the same was achieved at much lesser time (8-10 days compared to the earlier 12-15 days). The enhanced yield of the antibiotic strongly suggests that the fungus P. verruculosum MKH7 can be efficiently used for antibiotic production on a large scale.