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.

营养相互依赖性（综合）在通过使用合作细胞类型来改善生物技术过程方面的潜力尚未得到充分开发。到目前为止，酵母互养群落的设计需要广泛的遗传操作，因为大多数真核微生物营养缺陷型的共同接种不会导致合作生长。在这里，我们采用高通量表型筛选来系统地测试营养缺陷型酿酒酵母缺失突变体的成对组合。尽管大多数共培养对不会进入互养生长，但我们识别出 49 对自发形成互养、协同群落。我们表征了九种共培养物的稳定性和生长动态，并证明一对色氨酸营养缺陷型通过交换途径中间产物而不是最终产物来生长。然后，我们引入了在不同对营养缺陷型细胞之间分裂的丙二酸半醛生物合成途径，从而导致产量增加。我们的结果报告了酿酒酵母营养缺陷型自发形成的稳定的共养体，并说明了在合作的种内群落中分工的生物技术潜力。