Optimization Of the Culture Medium of Althiomycin-Producing Myxococcus stipitatus GL41 Using Plackett-Burman Design and Response Surface Methodology

Althiomycin is a thiazole antibiotic with broad-spectrum activity against Gram-positive and Gram-negative bacteria through protein synthesis inhibition at the site of the 50S ribosomal subunit. This study was conducted to improve althiomycin production in a wild myxobacterial strain (Myxococcus stipitatus GL41) by optimization of the fermentation medium. The Plackett-Burman design screened eleven critical factors that affect althiomycin content in extracts. The factors with significant effect (p < 0.05) were employed in the Box-Behnken model to clarify the interaction between the independent variables and identify the optimal value for each variable. Three factors (soluble starch, baker's yeast and hepes buffer) determined from the Plackett-Burman design regression analysis results showed significant effects on althiomycin production. The RSM model predicted the optimal fermentation medium's parameters, including 6.09 g/L of soluble starch, 4.05 g/L of baker's yeast, and 20.65 g/L of hepes buffer. Model validation was performed to estimate the althiomycin content showed that the value reached 3.3 mg/L, which is 4.7 times higher than the initial P medium. The mathematical model is well compatible with the experimental results showing that optimization of the fermentation medium by statistical algorithms is an effective solution to promote the production yield of natural compounds.