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The complexity of these changes is consistent with experimental observations, where cross-feeding strains harbor multiple mutations. The required metabolic changes are also no less complex than those observed for multiple other of the 56 cross feeding interactions we study. We discuss possible reasons why only two cross-feeding interactions have been discovered during experimental evolution and argue that multiple new cross-feeding interactions may await discovery.The metabolite acetyl-coenzyme A (acetyl-CoA) serves as an essential ele