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Escherichia coli remains the preferred recombinant expression host due to its well-characterized genetics and high-yield biosynthetic capacity, especially when dealing with biopharmaceuticals without complex post-translational modifications. However, a primary challenge in producing alphainterferons (IFN-α) - small therapeutic cytokines with potent antiviral and antineoplastic properties - is their propensity to aggregate into insoluble, inactive inclusion bodies. This necessitates costly and time-consuming denaturation and refolding protocols. The present review evaluates established strategies and recent advancements for the production of IFN-α in its native, soluble, and bioactive form. We discuss strategies such as the optimization of cultivation parameters, the deployment of engineered strains, the application of solubility-enhancing fusion partners, and periplasmic translocation strategies, among others. Additionally, we analyze downstream processing methodologies and analytical frameworks essential for verifying protein purity and conformational integrity. Finally, we identify current knowledge gaps and prospective research opportunities to further enhance soluble yields and process efficiency.
Bretas et al. (Wed,) studied this question.