Enhancing nemadectin production by Streptomyces cyaneogriseus ssp. noncyanogenus through quantitative evaluation and optimization of dissolved oxygen and shear force

In this study, effects of oxygen supply and shear stress on nemadectin production by Streptomyces cyaneogriseus ssp. noncyanogenus (S. cyaneogriseus) fermentation were investigated in shake flasks and 5-L bioreactors. Results showed sufficient dissolved oxygen level was essential for cells growth and nemadectin biosynthesis, while strong shear stress had negative impacts on both cell growth and nemadectin synthesis. Furthermore, when a combined paddle type was applied in culturing S. cyaneogriseus, the nemadectin production was increased by 23.6%. The influence of different agitation rates and paddle types on volumetric oxygen transfers coefficient (KLa) and shear stress were quantitatively studied through computational fluid dynamics simulation (CFD). The results of CFD revealed that high KLa as well as low shear stress co-existed under the combined impeller configuration at 650 rpm. This study is expected to be helpful to the scale-up of nemadectin fermentation and other stress-sensitive but high-oxygen-consumption filamentous microorganism.