Ogataea Yeast Platform for Recombinant Porcine Interferon-Alpha 1 Production: Toward Alternative Biotherapeutics for Swine Health Management

Infectious diseases in swine demand affordable, broad-spectrum antiviral strategies, such as recombinant interferons (IFNs). However, commercial yeast expression platforms often present financial barriers through licensing royalties. To provide a cost-effective regional alternative, we evaluated the domestic, thermotolerant yeast Ogataea polymorpha OP39 for producing recombinant porcine IFNs. Recombinant OP39 strains carrying expression cassettes for types I (poIFN-α1), II (poIFN-γ), and III (poIFN-λ3) IFNs were constructed and evaluated for their recombinant protein production performance. Following initial screening, the highest-yielding candidate, poIFN-α1, was selected for bioprocess optimization in shake flasks and a 5 L fermenter. Results showed that OP39 successfully secreted all three IFN types with a relatively low level of hyperglycosylation. Batch fermentation scale-up of r-poIFN-α1 achieved a final protein concentration of 0.45 ± 0.10 mg/mL. Crucially, the OP39-produced r-poIFN-α1 exhibited antiviral efficacy in vitro against economically important porcine viruses including African Swine Fever Virus, Porcine Epidemic Diarrhea Virus and Porcine Reproductive and Respiratory Syndrome Virus. Based on the proof-of-concept results in this study, the OP39 platform can be further developed into a viable, full freedom-to-operate system for local or regional biomanufacturing of biologically active veterinary therapeutics to support livestock health management.