Microbial engineering for the production of C2-C6 organic acids

Covering: up to the end of 2020 Organic acids, as building block compounds, have been widely used in food, pharmaceutical, plastic, and chemical industries. Until now, chemical synthesis is still the primary method for industrial-scale organic acid production. However, this process encounters some inevitable challenges, such as depletable petroleum resources, harsh reaction conditions and complex downstream processes. To solve these problems, microbial cell factories provide a promising approach for achieving the sustainable production of organic acids. However, some key metabolites in central carbon metabolism are strictly regulated by the network of cellular metabolism, resulting in the low productivity of organic acids. Thus, multiple metabolic engineering strategies have been developed to reprogram microbial cell factories to produce organic acids, including monocarboxylic acids, hydroxy carboxylic acids, amino carboxylic acids, dicarboxylic acids and monomeric units for polymers. These strategies mainly center on improving the catalytic efficiency of the enzymes to increase the conversion rate, balancing the multi-gene biosynthetic pathways to reduce the byproduct formation, strengthening the metabolic flux to promote the product biosynthesis, optimizing the metabolic network to adapt the environmental conditions and enhancing substrate utilization to broaden the substrate spectrum. Here, we describe the recent advances in producing C-2-C-6 organic acids by metabolic engineering strategies. In addition, we provide new insights as to when, what and how these strategies should be taken. Future challenges are also discussed in further advancing microbial engineering and establishing efficient biorefineries.