Fungal expression strategies for heterologous production of antimicrobial peptides

Antimicrobial peptides (AMPs) are promising candidates for next-generation therapeutics due to their broad-spectrum activity and reduced propensity for resistance, making them valuable in medicine, agriculture, and biotechnology. However, traditional AMP production methods including isolation from natural sources and chemical synthesis are costly, inefficient, and environmentally unsustainable, particularly for longer or post-translationally modified peptides. While heterologous expression has emerged as a scalable and versatile alternative, its success depends strongly on host selection and tailored optimisation strategies. This review examines recent advances in fungal systems as platforms for AMP production. Fungal systems, and particularly yeasts such as 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. We outline strain choice and engineering strategies that enhance AMP yield and bioactivity, including promoter and codon optimisation, secretion signal choice, fusion partners, and the construction of tandem or chimeric AMPs. By integrating current methodologies and case studies, this review aims to guide future efforts toward efficient, scalable, and commercially viable AMP manufacturing in fungal hosts, positioning fungal biotechnology as a key enabler in the development of next-generation antimicrobial solutions.