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.
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
Kate
K
Campbell
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
Jakob
J
Vowinckel
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
Michael
M
Mülleder
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
Silke
S
Malmsheimer
The Wellcome Trust Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.
Nicola
N
Lawrence
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
Enrica
E
Calvani
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
Leonor
L
Miller-Fleming
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
Mohammad T
MT
Alam
Institute of Molecular Systems Biology, ETH Zürich, Zurich, Switzerland.
Stefan
S
Christen
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
Markus A
MA
Keller
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.|Mill Hill Laboratory, The Francis Crick Institute, London, United Kingdom.
Markus
http://orcid.org/0000-0001-9535-7413
M
Ralser
D000596:Amino Acids / Q000378:metabolism*; D018920:Coculture Techniques; D055442:Metabolome; D056265:Microbial Interactions; D050296:Microbial Viability; D012441:Saccharomyces cerevisiae / Q000254:growth & development* / Q000378:metabolism*
D000596:Amino Acids
cell biology; cellular heterogeneity; computational biology; cooperativity; metabolism; s.cerevisae; systems biology