Komagataella phaffii as a microbial cell factory for antimicrobial peptide production

In recent decades, the methylotrophic yeast Komagataella phaffii has emerged as a powerful host for the heterologous production of antimicrobial peptides (AMPs) as an economical and scalable platform. K. phaffii combines several important advantages for a recombinant expression system, such as rapid growth, high-density cell culture, efficient protein secretion, and the ability to perform essential post-translational modifications. The methanol-inducible AOX1 promoter (P_AOX1), generally employed through the pPICZalpha vector, allows strong and tightly regulated heterologous expression and is a central factor in the expression system of this yeast. However, several strategies have been employed to produce recombinant AMPs in K. phaffii, among them codon optimization, engineered methanol-resistant strains, alternative promoters, and the use of different secretory peptides. This review highlights the latest advances and practical considerations in the use of K. phaffii for AMP production, discussing challenges such as peptide stability, proteolytic degradation, and yield optimization. The insights provided contribute to the expansion of biotechnological applications of K. phaffii, reinforcing its potential as an efficient and safe platform for large-scale production of therapeutic AMPs.