Spontaneously established syntrophic yeast communities improve bioproduction

Abstract

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.

Simple phenylpropanoids: recent advances in biological activities, biosynthetic pathways, and microbial production

“…Efforts to construct a mutualistic relationship for the members of microbial consortia to form stable mutualistic consortia is a viable approach to improve these strategies. 216,220…”

A molecular toolkit of cross-feeding strains for engineering synthetic yeast communities

“…In a consortium of co-auxotrophic strains, the survival of each member is dependent on other members supplying a particular nutrient which the recipient itself cannot synthesize. These nutrients could be amino acids, nucleotides or other essential metabolites 15 – 17 . For example, a two-member Corynebacterium glutamicum co-culture was created consisting of l -leucine and l -arginine auxotrophs 18 , and various Escherichia coli co-cultures have been created in vivo or designed in silico, which have ranged from 2–14 auxotrophs 15 , 19 , 20 .…”

Visioning synthetic futures for yeast research within the context of current global techno‐political trends

“…The challenges inherent in synthetic yeast communities elevates the concepts of a pan-genome and minimal genome to a higher level of abstraction. Work undertaken on syntrophic communities is promising and provides another methodology for exploring the greater biological design spaces that accompany multi-species interactions and integrations (Aulakh et al, 2023). Despite these challenges, exploratory research in this area remain largely untapped and ripe for the development of 'new science', with the potential for untapped applications in the coming decades.…”