Diverse bacteria exhibit superadditive growth on mixed classes of carbon sources

Heterotrophic bacteria in nature encounter complex mixtures of functionally-distinct carbon sources, yet whether such diversity enhances growth yield across diverse taxa remains unknown. We grew dozens of strains from four phyla on defined mixtures representing five classes of carbon sources. Remarkably, many but not all strains exhibited superadditive growth on a dilute mixture of all 64 compounds--that is, yield exceeding the weighted sum of yields on more concentrated subsets of functionally-similar compounds. Using exometabolomics, pooled genetic screens, and proteomics, we find that superadditive growth is associated with enhanced carbon consumption in the mixed-class medium, combined with reduced dependence on amino acid and nucleotide biosynthesis. Moreover, superadditive growth was predictable from genomes within the tested strain panel and correlated with genomically encoded sugar-over-acid preference. These findings reveal a previously underrecognized axis of physiological variation among heterotrophs and open the door to understanding the biochemical and evolutionary basis of this divergence.