Automated adjustment of metabolic niches enables the control of natural and engineered microbial co-cultures.

Much attention has focused on understanding microbial interactions leading to stable co-cultures. In this work, substrate pulsing was performed to promote better control of the metabolic niches (MNs) corresponding to each species, leading to the continuous co-cultivation of diverse microbial organisms. We used a cell-machine interface, which allows adjustment of the temporal profile of two MNs according to a rhythm, ensuring the successive growth of two species, in our case, a yeast and a bacterium. The resulting approach, called 'automated adjustment of metabolic niches' (AAMN), was effective for stabilizing both cooperative and competitive co-cultures. AAMN can be considered an enabling technology for the deployment of co-cultures in bioprocesses, demonstrated here based on the continuous bioproduction of p-coumaric acid. The data accumulated suggest that AAMN could be used not only for a wider range of biological systems, but also to gain fundamental insights into microbial interaction mechanisms.