Environment Constrains Fitness Advantages of Division of Labor in Microbial Consortia Engineered for Metabolite Push or Pull Interactions.

Fitness benefits from division of labor are well documented in microbial consortia, but the dependency of the benefits on environmental context is poorly understood. Two synthetic Escherichia coli consortia were built to test the relationships between exchanged organic acid, local environment, and opportunity costs of different metabolic strategies. Opportunity costs quantify benefits not realized due to selecting one phenotype over another. The consortia catabolized glucose and exchanged either acetic or lactic acid to create producer-consumer food webs. The organic acids had different inhibitory properties and different opportunity costs associated with their positions in central metabolism. The exchanged metabolites modulated different consortial dynamics. The acetic acid-exchanging (AAE) consortium had a "push" interaction motif where acetic acid was secreted faster by the producer than the consumer imported it, while the lactic acid-exchanging (LAE) consortium had a "pull" interaction motif where the consumer imported lactic acid at a comparable rate to its production. The LAE consortium outperformed wild-type (WT) batch cultures under the environmental context of weakly buffered conditions, achieving a 55% increase in biomass titer, a 51% increase in biomass per proton yield, an 86% increase in substrate conversion, and the complete elimination of by-product accumulation all relative to the WT. However, the LAE consortium had the trade-off of a 42% lower specific growth rate. The AAE consortium did not outperform the WT in any considered performance metric. Performance advantages of the LAE consortium were sensitive to environment; increasing the medium buffering capacity negated the performance advantages compared to WT. IMPORTANCE Most naturally occurring microorganisms persist in consortia where metabolic interactions are common and often essential to ecosystem function. This study uses synthetic ecology to test how different cellular interaction motifs influence performance properties of consortia. Environmental context ultimately controlled the division of labor performance as shifts from weakly buffered to highly buffered conditions negated the benefits of the strategy. Understanding the limits of division of labor advances our understanding of natural community functioning, which is central to nutrient cycling and provides design rules for assembling consortia used in applied bioprocessing.

Role of resource allocation and transport in emergence of cross-feeding in microbial consortia.

Microbial communities that implement mutual cross-feeding are commonly observed in nature and with synthetic constructs in laboratory experiments. A mathematical model of competition in a chemostat is developed to investigate the role that resource allocation and transport of metabolites play in cooperation. The model contains four cell types that differ by whether they produce two, one, or none of two essential metabolites. Producing cell types may export these resources into the environment, and those that do not produce both metabolites must import the missing resource. The contribution to the emergence of a collaborative consortium of single resource producers from the transport rate of these metabolites and the type of transport used by the cell (active vs. passive) is studied. Multiple instances of bi-stability and tri-stability are observed, and the effect of the initial concentration of a non-cooperative cheater cell type on the final outcome of the competition is examined. When the cost of producing metabolites is introduced into the model, significant changes to the outcome of the competition are observed, including coexistence of multiple cell types.