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 adjust
ment 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.