Fungal systems emerge as scalable, cost-effective platforms for antimicrobial peptide production

The escalating crisis of antimicrobial resistance (AMR) necessitates novel therapeutic agents, with antimicrobial peptides (AMPs) showing significant promise due to their broad-spectrum activity and reduced resistance propensity. However, traditional AMP production via natural isolation or chemical synthesis is often costly, inefficient, and environmentally unsustainable, particularly for longer or post-translationally modified peptides. This creates a critical gap in scalable manufacturing, hindering the translation of AMPs into widespread clinical, agricultural, and biotechnological applications. Exploring efficient heterologous expression systems is crucial to overcome these production bottlenecks.

This comprehensive review synthesizes recent advances in leveraging fungal systems for the heterologous production of antimicrobial peptides (AMPs). The authors systematically examined various host selection criteria and tailored optimization strategies that enhance AMP yield and bioactivity. Key areas covered include the strategic choice of fungal strains (e.g., Pichia pastoris), genetic engineering techniques such as promoter and codon optimization, selection of appropriate secretion signals, and the utilization of fusion partners. The review also delved into advanced constructs like tandem or chimeric AMPs, integrating current methodologies and relevant case studies to provide a practical guide for future manufacturing efforts.

Fungal systems, particularly yeasts like Pichia pastoris, are identified as leading hosts for recombinant AMP production due to several inherent advantages. These include rapid growth rates, low-cost fermentation processes, robust secretion capacities, and crucially, the ability to perform essential post-translational modifications (PTMs) that are vital for AMP bioactivity. The review highlights that successful heterologous expression hinges on tailored optimization strategies. Specific engineering approaches discussed include optimizing promoter strength and codon usage to maximize gene expression, selecting efficient secretion signals to facilitate extracellular release, and employing fusion partners to improve stability or solubility. The construction of tandem or chimeric AMPs is also presented as a strategy to enhance overall yield and expand functional properties. These integrated strategies collectively position fungal biotechnology as a key enabler for next-generation antimicrobial solutions.

Fungal systems, especially Pichia pastoris, offer rapid growth, low-cost fermentation, secretion capacity, and the ability to perform key post-translational modifications (PTMs), making them leading hosts for recombinant AMPs.