As natural metabolites, organic acids have been widely applied in food, pharmaceutical, and bio-based materials industries. Particularly, the short-chain organic acids, including C2, C3, C4, C5, and C6 organic acids, are necessary intermediate metabolites in cells and are also alternatives to some commercial chemical products. As the necessary metabolites in cells, most major short-chain organic acids can be produced through microbial fermentation. Specifically, with the development of synthetic biology, metabolic engineering could endow cells with the ability to produce more short-chain organic acid products including propionic acid, pyruvate, lactic acid, 3-hydroxypropionic acid, malic acid, succinic acid, fumaric acid, butyric acid, itaconic acid, α-ketoglutaric acid, glutaric acid, citric acid, gluconic acid, muconic acid, adipic acid, xylonic acid, and so on. The recent advances in the biological production of short-chain organic acids, as well as the challenges and perspectives, are summarized in this review to promote the generation of microbial cell factories for the production of short-chain organic acids.Key points• Outlines the production strategy of short-chain organic acids• Provide guidance for efficient synthesis of short-chain organic acids• Impacts the necessary factor of acid resistance on the successful production of host cells.
Keywords: Acid tolerance; Biosynthetic pathways; Metabolic engineering; Organic acid biosensor; Short-chain organic acids.