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Original article (peer-reviewed)

Journal ISME Journal
Page(s) 1568 - 1578
Title of proceedings ISME Journal

Open Access

Type of Open Access Repository (Green Open Access)


Different microbial cells 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, it is often unclear why it occurs. Why would a cell partially consume a substrate and release an intermediate that would otherwise support its growth? We hypothesized that substrate cross-feeding eliminates intra-enzyme competition 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 intra-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 intra-enzyme competition and the inhibitory effects of intermediates could therefore be important for deciding how to best segregate different metabolic processes into different cells to optimize a desired biotransformation.