s41589-023-01341-2.pdf (17.21 MB)
Spontaneously established syntrophic yeast communities improve bioproduction.
journal contributionposted on 2023-07-27, 11:32 authored by Simran Kaur Aulakh, Lara Sellés Vidal, Eric J South, Huadong Peng, Sreejith Jayasree Varma, Lucia Herrera-Dominguez, Markus Ralser, Rodrigo Ledesma-Amaro
Nutritional codependence (syntrophy) has underexplored potential to improve biotechnological processes by using cooperating cell types. So far, design of yeast syntrophic communities has required extensive genetic manipulation, as the co-inoculation of most eukaryotic microbial auxotrophs does not result in cooperative growth. Here we employ high-throughput phenotypic screening to systematically test pairwise combinations of auxotrophic Saccharomyces cerevisiae deletion mutants. Although most coculture pairs do not enter syntrophic growth, we identify 49 pairs that spontaneously form syntrophic, synergistic communities. We characterized the stability and growth dynamics of nine cocultures and demonstrated that a pair of tryptophan auxotrophs grow by exchanging a pathway intermediate rather than end products. We then introduced a malonic semialdehyde biosynthesis pathway split between different pairs of auxotrophs, which resulted in increased production. Our results report the spontaneous formation of stable syntrophy in S. cerevisiae auxotrophs and illustrate the biotechnological potential of dividing labor in a cooperating intraspecies community.
Crick (Grant ID: 10134, Grant title: Ralser FC001134) Wellcome Trust (Grant ID: 200829/Z/16/Z, Grant title: WT 200829/Z/16/Z)