Recent progress in microbial succinic acid production: integrating genome engineering and fermentation strategies.

Abstract

Succinic acid is a four-carbon dicarboxylic acid and important platform chemical with diverse applications in food and feed, pharmaceutical, textile, and bio-based polymer industries. Growing demand for sustainable and economically viable production routes has stimulated increasing interest in microbial routes for succinic acid biosynthesis as an alternative to conventional petrochemical processes. This mini-review summarizes recent advances in microbial succinic acid production, with particular emphasis on strain development, metabolic engineering, and fermentation-process optimization. Significant progress has been achieved through engineering of both native producers, Actinobacillus succinogenes, Mannheimia succiniciproducens, and Corynebacterium glutamicum and non-native production hosts, such as Escherichia coli, Klebsiella oxytoca, and several yeast species, leading to marked improvements in succinate concentration, yield, and productivity. Emerging approaches, including adaptive-laboratory evolution, systems-level omics, and CRISPR-Cas9, have enabled more precise control of carbon flux toward succinic acid biosynthesis while improving cellular tolerance to low pH and elevated succinic acid concentrations. In parallel, advances in fermentation and bioprocess strategies, particularly low-pH fermentation and enhanced CO₂ fixation, together with the valorization of renewable feedstocks such as lignocellulosic hydrolysates, offer promising opportunities to improve process feasibility and sustainability. However, their economic competitiveness remains strongly influenced by feedstock pretreatment, hydrolysis, detoxification, fermentation performance, and downstream processing requirements. Finally, current challenges and future perspectives for industrial-scale succinic acid production are discussed, highlighting the importance of integrating strain engineering with innovative bioprocess design to develop robust, economically competitive, and environmentally sustainable production platforms.