Microbial Division of Labor: A Product-Inhibition Model for Cross-Feeding in Serial Batch Culture

Abstract

In microbial communities, like phytoplankton ecosystems, many diverse species stably coexist on only a few resources; however, this tremendous biodiversity is an apparent contradiction to the theoretical competitive exclusion principle: the number of coexisting species in an ecosystem cannot exceed the number of different resources. In order to better understand the implications of coexistence for biological applications, a refined understanding of this apparent discrepancy between observation and theory is necessary. A few metabolic models have been proposed to rationalize coexistence arising from cross-feeding in serial dilution cultures; however, these models oversimplify cellular metabolism, failing to distinguish internal (cellular) intermediate concentration from external (batch) concentration. In this work, I propose a simplified metabolic model with one resource, one metabolically-inhibiting intermediate, and two-energy producing reactions. Using this model, I simulated ecological competition and evolutionarily optimized a pair of cross-feeding species, in which each species specializes in a different energy-producing reaction. When intermediate transport was fast, the cross-feeding pair stably coexisted alongside a “generalist,” which performed both reactions. However, this cross-feeding pair went extinct after a “versatile” species, capable of drawing from the external intermediate pool, was introduced into the batch; the “generalist” and “versatile” invader coexisted without cross-feeding. These results suggest that cross-feeding mutualism is not stable in serial batch cultures with only one intermediate; furthermore, evolutionary optimization can yield coexisting pairs, in line with competitive exclusion for two resources.