Abstract

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, implying the absence of growth-relevant metabolite exchange capacities. Contrastingly, we find that cells within colonies maintain a rich exometabolome and prefer uptake of extracellular metabolites over self-synthesis, indicators of ongoing metabolite exchange. We conceived a system that begins with a self-supporting cell which grows autonomously into a heterogeneous community, only able to survive by exchanging histidine, leucine, uracil and methionine. Compensating for the progressive loss of prototrophy, resultant communities obtained an auxotrophic composition in a nutrition dependent manner, and achieved 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.

Article and author information

Author details

  1. Kate Campbell

    Department of Biochemistry, Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Jakob Vowinckel

    Department of Biochemistry, Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael Muelleder

    Department of Biochemistry, Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Silke Malmsheimer

    Department of Biochemistry, Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Nicola Lawrence

    The Wellcome Trust Gordon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Enrica Calvani

    Department of Biochemistry, Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Leonor Miller-Fleming

    Department of Biochemistry, Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Mohammad T Alam

    Deptartment of Biochemistry, Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Stefan Christen

    Institute of Molecular Systems Biology, Eidgenoessische Technische Hochschule, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  10. Markus A Keller

    Department of Biochemistry, Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Markus Ralser

    Department of Biochemistry, Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    mr559@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Mohan Balasubramanian, University of Warwick, United Kingdom

Version history

  1. Received: July 8, 2015
  2. Accepted: October 20, 2015
  3. Accepted Manuscript published: October 26, 2015 (version 1)
  4. Version of Record published: December 16, 2015 (version 2)

Copyright

© 2015, Campbell et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Kate Campbell
  2. Jakob Vowinckel
  3. Michael Muelleder
  4. Silke Malmsheimer
  5. Nicola Lawrence
  6. Enrica Calvani
  7. Leonor Miller-Fleming
  8. Mohammad T Alam
  9. Stefan Christen
  10. Markus A Keller
  11. Markus Ralser
(2015)
Self-establishing communities enable cooperative metabolite exchange in a eukaryote
eLife 4:e09943.
https://doi.org/10.7554/eLife.09943

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https://doi.org/10.7554/eLife.09943