Campbell, Kate Vowinckel, Jakob Mülleder, Michael Malmsheimer, Silke Lawrence, Nicola Calvani, Enrica Miller-Fleming, Leonor Alam, Mohammad T Christen, Stefan Keller, Markus A Ralser, Markus Self-establishing communities enable cooperative metabolite exchange in a eukaryote 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. cell biology;cellular heterogeneity;computational biology;cooperativity;metabolism;s.cerevisae;systems biology;Amino Acids;Coculture Techniques;Metabolome;Microbial Interactions;Microbial Viability;Saccharomyces cerevisiae;Ralser MC_UP_1202/8;0601 Biochemistry and Cell Biology 2020-07-09
    https://crick.figshare.com/articles/journal_contribution/Self-establishing_communities_enable_cooperative_metabolite_exchange_in_a_eukaryote/12631151