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The objective of this study was to develop an optimal combination of mineral salts in the fermentation medium for nosiheptide (Nsh) production using statistical methodologies. A Plackett-Burman design (PBD) was used to evaluate the impacts of eight mineral salts on Nsh production. The results showed that among the no-significant factors, CaCO3, and K2HPO4·3H2O had positive effects, whereas FeSO4·7H2O, CuSO4·5H2O, and ZnSO4·7H2O had negative effects on Nsh production. The other three significant factors (Na2SO4, MnSO4·H2O, and MgSO4·7H2O) were further optimized by using a five-level three-factor central composite design (CCD). Experimental data were fitted to a quadratic polynomial model, which provided an effective way to determine the interactive effect of metal salts on Nsh production. The optimal values were determined to be 2.63, 0.21, and 3.37 g/L, respectively. The model also ensured a good fitting of scale-up Nsh batch fermentation with a maximum production of 1501 mg/L, representing a 1.56-fold increase compared to the original standard condition. All these results revealed that statistical optimization methodology had the potential to achieve comprehensive optimization in Nsh fermentation behaviors, which indicates a possibility to establish economical large-scale production of Nsh.

Effect Analysis of Mineral Salt Concentrations on Nosiheptide Production by Streptomyces actuosus Z-10 Using Response Surface Methodology