Microgravity-induced constraints on melanin bioproduction: investigating E. coli metabolic responses aboard the international space station

Space biomanufacturing using engineered microbes offers a sustainable approach for producing biomaterials, pharmaceuticals, and essential metabolites, critical for long-duration space missions. However, microgravity-induced physiological changes can alter microbial metabolism and biosynthetic efficiency. This study investigated the effects of microgravity on melanin biosynthesis in non-motile Escherichia coli aboard the International Space Station (ISS). Despite expressing functional tyrosinase, ISS-grown E. coli exhibited significantly lower melanin production than ground controls. Differential pulse voltammetry revealed high extracellular tyrosine in ISS samples, indicating inefficient substrate catalysis. Low Shear Modeled Microgravity (LSMMG) experiments in the Rotating Wall Vessel bioreactor confirmed reduced melanin production and bacterial viability. Proteomic profiling identified increased expression of membrane, transport, and stress-related proteins, while metabolomic analysis showed elevated trehalose and decreased glutathione, indicating oxidative stress and perturbed redox homeostasis. These findings highlight the impact of microgravity on microbial metabolism and provide insights for optimizing microbial biomanufacturing in extraterrestrial environments.