代谢工程改造大肠杆菌利用脂肪酸合成己二酸

Metabolic Engineering of Escherichia coli for Synthesis of Adipic Acid from Fatty Acids

己二酸作为生产尼龙、化纤和工程塑料等聚合物的单体,在食品、医药、塑料和化工行业具有广泛的应用。目前,己二酸的生物合成主要利用可食用原料,碳原子损失较多,造成己二酸产率较低。为解决上述问题,设计和重构以脂肪酸为原料的己二酸合成新路径,提高己二酸的理论得率;其次,强化本源的β-氧化路径和引入异源的ω-氧化路径;增强细胞对脂肪酸的利用能力;再次,借助系统代谢工程策略,进一步优化己二酸合成路径。最后,经发酵条件优化,最优工程菌Escherichia coli AA0304能够产生1.32 g/L己二酸。上述研究结果为利用废弃脂肪酸类化合物生产高价值化学品奠定了良好的基础。

Adipic acid,as the monomer for manufacturing polymers such as nylon,fiber and plastics,has broad applications in food,pharmaceutical,plastics,and chemical industries.At present,low-level yield of adipic acid generated from food feedstocks was mainly due to the carbon atom loss.To tackle this issue,an artificial adipic acid biosynthesis pathway for obtaining the highest theoretical adipic acid yield from palmitic acid was designed and constructed.Then,cell utilization for fatty acids was improved by enhancing endogenousβ-oxidation pathway and introducing heterogenousω-oxidation pathway.Furthermore,various strategies of system metabolic engineering were used for further optimizing adipic acid biosynthesis pathway.Finally,the optimal recombinant strain Escherichia coli AA0304 produced 1.32 g/L adipic acid by optimizing fermentation conditions.Therefore,this synthetic platform could lay a good foundation for the production of high-value chemicals from waste oleaginous feedstocks.