a programmable escherichia coli consortium via tunable symbiosis一个可编程的大肠杆菌财团通过可调的共生关系.pdfVIP

A Programmable Escherichia coli Consortium via Tunable Symbiosis 1,2 2 2 1,2,3 Alissa Kerner , Jihyang Park , Audra Williams , Xiaoxia Nina Lin * 1 Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America, 2 Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America, 3 Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America Abstract Synthetic microbial consortia that can mimic natural systems have the potential to become a powerful biotechnology for various applications. One highly desirable feature of these consortia is that they can be precisely regulated. In this work we designed a programmable, symbiotic circuit that enables continuous tuning of the growth rate and composition of a synthetic consortium. We implemented our general design through the cross-feeding of tryptophan and tyrosine by two E. coli auxotrophs. By regulating the expression of genes related to the export or production of these amino acids, we were able to tune the metabolite exchanges and achieve a wide range of growth rates and strain ratios. In addition, by inverting the relationship of growth/ratio vs. inducer concentrations, we were able to ‘‘program’’ the co-culture for pre-specified attributes with the proper addition of inducing chemicals. This programmable proof-of-concept circuit or its variants can be applied to more complex systems where precise tuning of the consortium would facilitate the optimization of specific objectives, such as increasing the overall efficiency of microbial production of biofuels or pharmaceuticals. Citation: Kerner A, Park J, Willia