Scaling-up strategies for controllable biosynthetic ZnO NPs using cell free-extract of endophytic Streptomyces albus: characterization, statistical optimization, and biomedical activities evaluation

In this study, we identified a suitable precursor and good cellular compartmentalization for enhancing bioactive metabolites to produce biosynthetic zinc oxide nanoparticles (ZnO NPs). An effective medium for cultivating endophytic Streptomyces albus strain E56 was selected using several optimized approaches in order to maximize the yield of biosynthetic ZnO NPs. The highest biosynthetic ZnO NPs yield (4.63 g/L) was obtained when pipetting the mixed cell-free fractions with 100 mM of zinc sulfate as a precursor. The generation of biosynthetic ZnO NPs was quickly verified using a colored solution (white color) and UV–Visible spectroscopy (maximum peak, at 320 nm). On a small scale, the Taguchi method was applied to improve the culture medium for culturing the strain E56. As a result, its cell-dry weight was 3.85 times that of the control condition. And then the biosynthesis of ZnO NPs (7.59 g/L) was increased by 1.6 times. Furthermore, by using the Plackett–Burman design to improve the utilized biogenesis pathway, the biosynthesis of ZnO NPs (18.76 g/L) was increased by 4.3 times. To find the best growth production line, we used batch and fed batch fermentation modes to gradually scale up biomass output. All kinetics of studied cell growth were evaluated during fed-batch fermentation as follows: biomass yield was 271.45 g/L, yield coefficient was 94.25 g/g, and ZnO NPs yield was 345.32 g/L. In vitro, the effects of various dosages of the controllable biosynthetic ZnO NPs as antimicrobial and anticancer agents were also investigated. The treatments with controllable biosynthetic ZnO NPs had a significant impact on all the examined multidrug-resistant human pathogens as well as cancer cells.