title: Metabolic engineering in the biotechnological production of organic acids in the tricarboxylic acid cycle of microorganisms: Advances and prospects.
abstract: Organic acids, which are chemically synthesized, are also natural intermediates in the metabolic pathways of microorganisms, among which the tricarboxylic acid (TCA) cycle is the most crucial route existing in almost all living organisms. Organic acids in the TCA cycle include citric acid, α-ketoglutaric acid, succinic acid, fumaric acid, l-malic acid, and oxaloacetate, which are building-block chemicals with wide applications and huge markets. In this review, we summarize the synthesis pathways of these organic acids and review recent advances in metabolic engineering strategies that enhance organic acid production. We also propose further improvements for the production of organic acids with systems and synthetic biology-guided metabolic engineering strategies.
authors.affiliation: Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China; Synergetic Innovation Center of Food Safety and Nutrition, Wuxi 214122, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Yin
authors.affiliation: Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; Synergetic Innovation Center of Food Safety and Nutrition, Wuxi 214122, China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Chemical and Biomolecular Engineering, GA Institute of Technology, Atlanta 30332, USA.
authors.forename: Hyun-Dong
authors.initials: HD
authors.lastname: Shin
authors.affiliation: Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; Synergetic Innovation Center of Food Safety and Nutrition, Wuxi 214122, China.
authors.forename: Guocheng
authors.initials: G
authors.lastname: Du
authors.affiliation: Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China; Synergetic Innovation Center of Food Safety and Nutrition, Wuxi 214122, China. Electronic address: longliu@jiangnan.edu.cn.
authors.forename: Long
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; National Engineering of Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China. Electronic address: jchen@jiangnan.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
mesh_terms: D001709:Biotechnology; D002952:Citric Acid Cycle; D003998:Dicarboxylic Acids; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D060847:Metabolic Engineering; D012233:Rhizopus / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: D003998:Dicarboxylic Acids
keywords: C(4)-dicarboxylic acid; Citric acid; Fumaric acid; Metabolic engineering; Oxaloacetate; Succinic acid; Tricarboxylic acid (TCA) cycle; l-Malic acid; α-Ketoglutaric acid