Segregating metabolic processes into different microbial cells accelerates the consumption of inhibitory substrates

ISME J. 2016 Jul;10(7):1568-78. doi: 10.1038/ismej.2015.243. Epub 2016 Jan 15.


Different microbial cell types typically specialize at performing different metabolic processes. A canonical example is substrate cross-feeding, where one cell type consumes a primary substrate into an intermediate and another cell type consumes the intermediate. While substrate cross-feeding is widely observed, its consequences on ecosystem processes is often unclear. How does substrate cross-feeding affect the rate or extent of substrate consumption? We hypothesized that substrate cross-feeding eliminates competition between different enzymes and reduces the accumulation of growth-inhibiting intermediates, thus accelerating substrate consumption. We tested this hypothesis using isogenic mutants of the bacterium Pseudomonas stutzeri that either completely consume nitrate to dinitrogen gas or cross-feed the intermediate nitrite. We demonstrate that nitrite cross-feeding eliminates inter-enzyme competition and, in turn, reduces nitrite accumulation. We further demonstrate that nitrite cross-feeding accelerates substrate consumption, but only when nitrite has growth-inhibiting effects. Knowledge about inter-enzyme competition and the inhibitory effects of intermediates could therefore be important for deciding how to best segregate different metabolic processes into different microbial cell types to optimize a desired biotransformation.

MeSH terms

  • Mutation
  • Nitrates / metabolism*
  • Nitrites / metabolism*
  • Pseudomonas / genetics
  • Pseudomonas / metabolism*


  • Nitrates
  • Nitrites