Semi-industrial Bio-fabrication of ZnO/MnO₂ Nanocomposite Using Endophytic Streptomyces coelicolor: Characterization, Statistical Design, Exponential Pulse Fed-Batch Fermentation, and Its Antimicrobial Application

In our study, we examined how well six Streptomyces strains bio-fabricated ZnONPs, MnONPs, and/or ZnO/MnO₂ nanocomposite. The most potent strain that generated efficient antimicrobial nanoparticles was then picked to increase the production of those particles in a semi-industrial pilot plant unit. Consequently, the intracellular extract of endophytic Streptomyces coelicolor strain E72 was used to achieve the bio-fabrication reaction of the spherical ZnO/MnO₂ nanocomposite (6–18 nm). The bio-fabricated ZnO/MnO₂ nanocomposite was validated and characterized using FTIR, XRD, SEM, TEM, TGA, and EDS analyses. Additionally, the production of this ZnO/MnO₂ nanocomponent was scaled up to a pilot plant unit with a semi-industrial size. The Plackett–Burman experimental method was used to maximize the production of ZnO/MnO₂ nanocomposites, which had increased 2.7-fold from their initial state. The bio-fabricated ZnO/MnO₂ nanocomposite was subsequently scaled up 31.25 times using an exponential pulse-feeding fermentation technique in a 70-L bioreactor. This ZnO/MnO₂ nanocomposite exhibited effective antimicrobial efficacy against all tested antibiotic-resistant human pathogens. The antimicrobial effects against Salmonella paratyphi (53.17 ± 2.8 mm) and Candida albicans (50.2 ± 1.01 mm) were the most potent at 90 and 130 µg/ml of ZnO/MnO₂ nanocomposite, respectively. This is the first full explanation of the ZnO/MnO₂ nanocomposite bio-fabrication at a semi-industrial scale employing endophytic strain E72 extract as a reducing/capping agent that reacted with MnCl₂·4H₂O and Zn (CH₃COO)₂·2H₂O as precursors. This bio-fabricated ZnO/MnO₂ nanocomposite has the potential to be utilized in the development of pharmaceuticals, cosmetics, wound dressings, and burn therapy due to its powerful antimicrobial capabilities.