α-酮异己酸的生物合成研究进展

Recent advances in microbial synthesis of α-ketoisocaproate

α-酮异己酸是重要有机酸、药用氨基酸合成前体、新陈代谢调节因子和治疗药物,其生物合成路径条件温和,环境友好。本文对α-酮异己酸的生理功能和体内代谢机理进行了归纳,并着重对其生物合成路径的研究进展进行了综述。现有研究表明,α-酮异己酸可用葡萄糖为底物,通过代谢工程改造的谷氨酸棒杆菌或大肠杆菌工程菌发酵合成,但产物浓度较低;或以L-亮氨酸为底物,经氨基酸转氨酶、氧化酶、脱氨酶、重组工程菌或全细胞催化转化合成,产物浓度较高。α-酮异己酸高产菌株的筛选、利用代谢工程方法对菌株进行改造以构建高效工程菌、发酵与分离提取工艺优化等问题,是今后需要研究的重点。

α-Ketoisocaproate(KIC)is not only an important organic acid and key precursor of branched chain amino acids for pharmaceuticals,but also a metabolic regulator and therapeutic agent.Biosynthesis pathway for the production of KIC has advantages of the mild reaction conditions and environment-friendly processes.In this work,the advances of the important physiological properties,the metabolisms and the biosynthetic pathways of KIC,were summarized.According to the references,two biosynthetic pathways are available for the preparation of KIC.The first one is the microbial fermentation approach using the strains of Corynebacterium glutamicum by metabolic engineering or recombinant Escherichia coli with glucose as the substrate,where the yield is low.The another is the enzymatic catalyzing using amino acid aminotransferases,oxidases or deaminases,the whole-cell bioconversion and the recombinant engineering strains using L-leucine as the substrate,where the yield is slightly high.Issues regarding the metabolic engineering improvement of the yield of KIC,the biosynthesis pathway,and the advanced fermentation and separation techniques,were proposed and considered as the important future research directions.