Self-establishing communities enable cooperative metabolite exchange in a eukaryote

Elife. 2015 Oct 26;4:e09943. doi: 10.7554/eLife.09943.


Metabolite exchange among co-growing cells is frequent by nature, however, is not necessarily occurring at growth-relevant quantities indicative of non-cell-autonomous metabolic function. Complementary auxotrophs of Saccharomyces cerevisiae amino acid and nucleotide metabolism regularly fail to compensate for each other's deficiencies upon co-culturing, a situation which implied the absence of growth-relevant metabolite exchange interactions. Contrastingly, we find that yeast colonies maintain a rich exometabolome and that cells prefer the uptake of extracellular metabolites over self-synthesis, indicators of ongoing metabolite exchange. We conceived a system that circumvents co-culturing and begins with a self-supporting cell that grows autonomously into a heterogeneous community, only able to survive by exchanging histidine, leucine, uracil, and methionine. Compensating for the progressive loss of prototrophy, self-establishing communities successfully obtained an auxotrophic composition in a nutrition-dependent manner, maintaining a wild-type like exometabolome, growth parameters, and cell viability. Yeast, as a eukaryotic model, thus possesses extensive capacity for growth-relevant metabolite exchange and readily cooperates in metabolism within progressively establishing communities.

Keywords: cell biology; cellular heterogeneity; computational biology; cooperativity; metabolism; s.cerevisae; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism*
  • Coculture Techniques
  • Metabolome
  • Microbial Interactions*
  • Microbial Viability
  • Saccharomyces cerevisiae / growth & development*
  • Saccharomyces cerevisiae / metabolism*


  • Amino Acids

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.