Engineering microorganisms for the biosynthesis of dicarboxylic acids

Dicarboxylic acids (DCAs) are important commodity chemicals which have been widely applied in polymer, food and pharmaceutical industries. Biosynthesis of DCAs from renewable carbon sources represents a promising alternative to chemical synthesis. Over the years, the recombinant strains have been constructed to produce an increasing number of DCAs. In this review, recent advances on the microbial synthesis of various DCAs have been summarized and categorized into three groups: the tricarboxylic acid cycle-derived, lysine metabolism-related, and aromatic compounds degradation-derived DCAs. We focused mainly on the metabolic engineering and synthetic biology strategies for improving the production efficiency, including metabolic flux analysis, fine-tuning of gene expression, cofactor balancing, metabolic compartmentalization, dynamic regulation and co-culture to regulate the production at multiple levels. The current challenges and perspectives have also been discussed.