Itaconic acid biomanufacturing: metabolic engineering and green process development.

Abstract

Itaconic acid (IA), an important unsaturated dicarboxylic acid, finds wide applications in industry, medicine, food, and energy. Biotechnological production of IA offers advantages in sustainability, process controllability, and the potential for high titers in selected hosts, although cost competitiveness remains a major barrier to industrial deployment. However, several challenges still hinder its large-scale industrial production, including: low substrate utilization efficiency, difficulty in pathway regulation, downstream separation bottlenecks, and environmental concerns. To address these challenges and further improve IA production through metabolic engineering, this review summarizes recent advances and key technologies in IA biosynthesis. Engineering strategies for de novo IA production were analyzed, the application of whole-cell catalysis and fermentation process optimization to enhance IA yield was discussed, and the use of renewable resources as substrates for IA production was reviewed. In addition, the prospects of AI-assisted strain engineering and green, low-carbon process technologies for IA biosynthesis were examined. These insights provide valuable guidance for understanding metabolic engineering strategies and bioprocess innovations aimed at improving IA production in alignment with sustainable and low-carbon objectives.