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

Ashley E. Beck, Kathryn Pintar, Diana Schepens, Ashley Schrammeck, Timothy Johnson, Alissa Bleem, Martina Du, William R. Harcombe, Hans C. Bernstein, Jeffrey J. Heys, Tomas Gedeon, Ross P. Carlson

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2 Scopus citations


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.

Original languageEnglish (US)
Issue number4
StatePublished - Aug 2022

Bibliographical note

Funding Information:
The study was supported by NSF awards DMS 1361240 and DGE 0654336 and NIH award U01EB019416. A.E.B. was supported in part by the USDA National Institute of Food and Agriculture (Hatch 1018813) and the M.J. Murdock Charitable Trust Biology Start-up Grant to Carroll College. Undergraduate researchers K.P., A.S., T.J., A.B., and M.D. were supported in part by the Montana State Undergraduate Scholars program and the National Institute of General Medical Sciences of the NIH under award no. P20GM103474.

Publisher Copyright:
© 2022 American Society for Microbiology. All rights reserved.


  • consortia
  • division of labor
  • metabolite inhibition
  • synthetic ecology


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