Biotechnological Advances in Microbial Kojic Acid Production and Sustainable Industrial Applications

Abstract

Kojic acid is an industrially important fungal secondary metabolite widely utilised in the cosmetic, pharmaceutical, and food industries due to its tyrosinase inhibitory, antioxidant, and metal-chelating properties. The increasing commercial demand for naturally derived kojic acid is constrained by limitations associated with substrate costs, fermentation efficiency, and downstream processing. Microbial fermentation using Aspergillus species continues to represent the most practical production route due to its environmental compatibility and scalability. This review critically evaluates recent advances in microbial kojic acid production with an emphasis on biosynthetic regulation, fermentation technologies, strain engineering, downstream processing, and sustainable bioprocessing strategies. Particular attention is given to submerged and solid-state fermentation systems, optimisation of physicochemical parameters, and the utilisation of agro-industrial residues as low-cost substrates. Recent advances in metabolic engineering, including CRISPR-assisted genome modification and pathway optimisation in engineered Aspergillus strains, are also discussed in relation to productivity enhancement and metabolic regulation. In addition, the review highlights emerging industrial applications of kojic acid and its derivatives in nanotechnology-based delivery systems, antimicrobial biomaterials, food preservation, and biomedical formulations. Recent developments in green cosmetic formulations, hydrogel-based delivery systems, niosomal encapsulation, and biorefinery-integrated fermentation have further expanded the industrial significance of kojic acid. Advanced formulation technologies improve compound stability, bioavailability, and skin permeability while supporting environmentally sustainable production systems. Despite substantial progress, industrial production continues to face limitations associated with oxygen transfer, substrate inconsistency, purification costs, and process scalability.  Future research should therefore focus on integrating systems biology, smart bioprocess control, sustainable feedstock utilisation, and circular bioeconomy principles to establish economically viable and environmentally sustainable production platforms for kojic acid.