Microbial Biosynthesis of L-Malic Acid and Related Metabolic Engineering Strategies: Advances and Prospects

Malic acid, a four-carbon dicarboxylic acid, is widely used in the food, chemical and medical industries. As an intermediate of the TCA cycle, malic acid is one of the most promising building block chemicals that can be produced from renewable sources. To date, chemical synthesis or enzymatic conversion of petrochemical feedstocks are still the dominant mode for malic acid production. However, with increasing concerns surrounding environmental issues in recent years, microbial fermentation for the production of L-malic acid was extensively explored as an eco-friendly production process. The rapid development of genetic engineering has resulted in some promising strains suitable for large-scale bio-based production of malic acid. This review offers a comprehensive overview of the most recent developments, including a spectrum of wild-type, mutant, laboratory-evolved and metabolically engineered microorganisms for malic acid production. The technological progress in the fermentative production of malic acid is presented. Metabolic engineering strategies for malic acid production in various microorganisms are particularly reviewed. Biosynthetic pathways, transport of malic acid, elimination of byproducts and enhancement of metabolic fluxes are discussed and compared as strategies for improving malic acid production, thus providing insights into the current state of malic acid production, as well as further research directions for more efficient and economical microbial malic acid production.