Syntrophic exchange in synthetic microbial communities.
Metabolic crossfeeding is an important process that can broadly shape microbial communities. However, little is known about specific crossfeeding principles that drive the formation and maintenance of individuals within a mixed population. Here, we devised a series of synthetic syntrophic communities to probe the complex interactions underlying metabolic exchange of amino acids. We experimentally analyzed multimember, multidimensional communities of Escherichia coli of increasing sophistication to assess the outcomes of synergistic crossfeeding. We find that biosynthetically costly amino acids including methionine, lysine, isoleucine, arginine, and aromatics, tend to promote stronger cooperative interactions than amino acids that are cheaper to produce. Furthermore, cells that share common intermediates along branching pathways yielded more synergistic growth, but exhibited many instances of both positive and negative epistasis when these interactions scaled to higher dimensions. In more complex communities, we find certain members exhibiting keystone species-like behavior that drastically impact the community dynamics. Based on comparative genomic analysis of >6,000 sequenced bacteria from diverse environments, we present evidence suggesting that amino acid biosynthesis has been broadly optimized to reduce individual metabolic burden in favor of enhanced crossfeeding to support synergistic growth across the biosphere. These results improve our basic understanding of microbial syntrophy while also highlighting the utility and limitations of current modeling approaches to describe the dynamic complexities underlying microbial ecosystems. This work sets the foundation for future endeavors to resolve key questions in microbial ecology and evolution, and presents a platform to develop better and more robust engineered synthetic communities for industrial biotechnology.
Department of Biomedical Engineering, Boston University, Boston, MA 02215;Department of Genetics, Harvard Medical School, Boston, MA 02115;
Michael T
MT
Mee
Department of Biomedical Engineering, Boston University, Boston, MA 02215;Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115;Howard Hughes Medical Institute andCenter of Synthetic Biology, Boston University, Boston, MA 02215; and.
James J
JJ
Collins
Department of Genetics, Harvard Medical School, Boston, MA 02115;Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115; gchurch@genetics.med.harvard.edu hw2429@c2b2.columbia.edu.
George M
GM
Church
Department of Systems Biology, Columbia University, New York, NY 10032 gchurch@genetics.med.harvard.edu hw2429@c2b2.columbia.edu.
Harris H
HH
Wang
D000596:Amino Acids / Q000096:biosynthesis; D000601:Amino Acids, Essential / Q000096:biosynthesis*; D001419:Bacteria / Q000235:genetics* / Q000378:metabolism; D018920:Coculture Techniques; D004463:Ecology; D017753:Ecosystem; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D056265:Microbial Interactions; D008954:Models, Biological; D010802:Phylogeny; D013696:Temperature
D000596:Amino Acids; D000601:Amino Acids, Essential
amino acid exchange; population modeling; synthetic ecosystem