Comparative analysis of the chemical and biochemical synthesis of keto acids

Keto acids are essential organic acids that are widely applied in pharmaceuticals, cosmetics, food, beverages, and feed additives as well as chemical synthesis. Currently, most keto acids on the market are prepared via chemical synthesis. The biochemical synthesis of keto acids has been discovered with the development of metabolic engineering and applied toward the production of specific keto acids from renewable carbohydrates using different metabolic engineering strategies in microbes. In this review, we provide a systematic summary of the types and applications of keto acids, and then summarize and compare the chemical and biochemical synthesis routes used for the production of typical keto acids, including pyruvic acid, oxaloacetic acid, α-oxobutanoic acid, acetoacetic acid, ketoglutaric acid, levulinic acid, 5-aminolevulinic acid, α-ketoisovaleric acid, α-keto-γ-methylthiobutyric acid, α-ketoisocaproic acid, 2-keto-L-gulonic acid, 2-keto-D-gluconic acid, 5-keto-D-gluconic acid, and phenylpyruvic acid. We also describe the current challenges for the industrial-scale production of keto acids and further strategies used to accelerate the green production of keto acids via biochemical routes.