Measuring intracellular fluxes by 13C metabolic flux analysis (13C-MFA) has become a key activity in metabolic engineering, biotechnology and medicine. Here, I will present new advances in 13C-MFA that have extended the scope of this technology to more complex biological systems. Specifically, I will demonstrate a new approach that we have developed for elucidating syntrophic interactions in microbial communities. Syntrophy (or cross-feeding) is the co-existence of two or more microbes whereby one feeds off the products of the other. To dissect such interactions in complex communities we have developed a multi-scale 13C-MFA modeling approach that allows us, for the first time, to quantify metabolic fluxes, metabolite cross-feeding, and population dynamics.
Overall, the methods we have developed have opened new areas of investigation, allowing us to dissect systems that are of significant importance to biology. More broadly, by better understanding coordinated relationships at the genetic, molecular, cellular, and systems levels we are generating new knowledge on microbial syntrophy that enables us to ensemble synergistic interactions in engineered microbial communities for applications in biotechnology and medicine.