Applying pathway engineering to enhance production of alpha-ketoglutarate in Yarrowia lipolytica

摘要

alpha-Ketoglutarate (alpha-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, alpha-KG occupies key positions in the tricarboxylate cycle (TCA cycle) and amino acid metabolic pathway, the over-accumulation of alpha-KG is restricted both by tighter carbon and nitrogen regulation process. Biotechnology production of alpha-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 alpha-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 alpha-KG, blocking competing pathways, regenerating of co-factors and regulating of carboxylate transporters to facilitate production and accumulation of alpha-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 alpha-KG production.