title: Applying pathway engineering to enhance production of alpha-ketoglutarate in Yarrowia lipolytica.
abstract: α-Ketoglutarate (α-KG), one of short-chain carboxylates of high commercial relevance, has been widely used in food, medicine, chemical, and cosmetic fields. Compared to other carboxylates, α-KG occupies key positions in the tricarboxylate cycle (TCA cycle) and amino acid metabolic pathway, the over-accumulation of α-KG is restricted both by tighter carbon and nitrogen regulation process. Biotechnology production of α-KG on large industrial level has been impeded by many obstacles. This review aims at highlighting and stating recent efforts toward improving the yield and titer of α-KG in the strains of Yarrowia lipolytica to reach industrial relevance. Fermentation process optimization concerning feedstock utilization, dissolved oxygen controlling, pH manipulation and establishment of fed-batch process, have been assessed and evaluated. Moreover, pathway engineering routes have been applied for enhancing carbon commitment to α-KG, blocking competing pathways, regenerating of co-factors and regulating of carboxylate transporters to facilitate production and accumulation of α-KG. Although no engineered strain can satisfy the requirements of industrial production relevance to date, these strategies provide many clues for accelerating strain development for α-KG production.
authors: Department of Biotechnology and Bioengineering, School of Chemical Engineering and Key Laboratory of Fujian Province for Biochemical Technology, National Huaqiao University, 668 Jimei Road, Amoy, Fujian, 361021, China. guohw@hqu.edu.cn.
authors: Hongwei
authors: H
authors: Guo
authors: Department of Biotechnology and Bioengineering, School of Chemical Engineering and Key Laboratory of Fujian Province for Biochemical Technology, National Huaqiao University, 668 Jimei Road, Amoy, Fujian, 361021, China.
authors: Shaojie
authors: S
authors: Su
authors: UMR782, Génie et Microbiologie des Procédés Alimentaires, INRA/CNRS/AgroPan's Tech, CBAI, BP 01, F-78850, Thiverval-Grignon, France.
authors: Catherine
authors: C
authors: Madzak
authors: School of Biotechnology and Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China.
authors: Jingwen
authors: J
authors: Zhou
authors: Department of Biotechnology and Bioengineering, School of Chemical Engineering and Key Laboratory of Fujian Province for Biochemical Technology, National Huaqiao University, 668 Jimei Road, Amoy, Fujian, 361021, China. chenhw@hqu.edu.cn.
authors: Hongwen
authors: H
authors: Chen
authors: Department of Biotechnology and Bioengineering, School of Chemical Engineering and Key Laboratory of Fujian Province for Biochemical Technology, National Huaqiao University, 668 Jimei Road, Amoy, Fujian, 361021, China.
authors: Guo
authors: G
authors: Chen
mesh_terms: D003470:Culture Media / Q000737:chemistry; D005285:Fermentation; D007656:Ketoglutaric Acids / Q000378:metabolism*; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D025062:Yarrowia / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*
chemical_list: D003470:Culture Media; D007656:Ketoglutaric Acids
keywords: Pathway engineering; TCA cycle; Yarrowia lipolytica; α-Ketoglutarate