(6fe) Co-culture based modular engineering for aromatic and aromatic-derived compound production in Escherichia coli

Traditional metabolic engineering studies focus on engineering target metabolic pathways in one single cell. Despite having gained many successes, this approach suffers from several disadvantages which limit its wide application in the future metabolic engineering research. Here, we developed a novel bacterium E. coli-E. coli co-culture approach to completely modularize and optimize the biosynthetic pathway in two separate cells. In particular, a membrane-bound transporter was utilized to facilitate the intermediate mass transfer between the two modules/cells so that the two cells worked as an integrated whole. The co-culture system was shown to produce value-added aromatic and aromatic-derived compounds with high titer and yield. Moreover, the co-culture system can be engineered to efficiently utilize sugar mixtures, which is challenging for the single cell strategy. The established method in this study offers a novel perspective for conducting metabolic engineering studies in the future.