An interspecies malate–pyruvate shuttle reconciles redox imbalance in an anaerobic microbial community

Po Hsiang Wang, Kevin Correia, Han Chen Ho, Naveen Venayak, Kayla Nemr, Robert Flick, Radhakrishnan Mahadevan, Elizabeth A. Edwards

研究成果: 雜誌貢獻期刊論文同行評審

11 引文 斯高帕斯(Scopus)


Microbes in ecosystems often develop coordinated metabolic interactions. Therefore, understanding metabolic interdependencies between microbes is critical to deciphering ecosystem function. In this study, we sought to deconstruct metabolic interdependencies in organohalide-respiring consortium ACT-3 containing Dehalobacter restrictus using a combination of metabolic modeling and experimental validation. D. restrictus possesses a complete set of genes for amino acid biosynthesis yet when grown in isolation requires amino acid supplementation. We reconciled this discrepancy using flux balance analysis considering cofactor availability, enzyme promiscuity, and shared protein expression patterns for several D. restrictus strains. Experimentally, 13 C incorporation assays, growth assays, and metabolite analysis of D. restrictus strain PER-K23 cultures were performed to validate the model predictions. The model resolved that the amino acid dependency of D. restrictus resulted from restricted NADPH regeneration and predicted that malate supplementation would replenish intracellular NADPH. Interestingly, we observed unexpected export of pyruvate and glutamate in parallel to malate consumption in strain PER-K23 cultures. Further experimental analysis using the ACT-3 transfer cultures suggested the occurrence of an interspecies malate–pyruvate shuttle reconciling a redox imbalance, reminiscent of the mitochondrial malate shunt pathway in eukaryotic cells. Altogether, this study suggests that redox imbalance and metabolic complementarity are important driving forces for metabolite exchange in anaerobic microbial communities.

頁(從 - 到)1042-1055
期刊ISME Journal
出版狀態已出版 - 1 4月 2019


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