Dietary- and host-derived metabolites are used by diverse gut bacteria for anaerobic respiration
Respiratory reductases enable microorganisms to use molecules present in anaerobic ecosystems as energy-generating respiratory electron acceptors. Here we identify three taxonomically distinct families of human gut bacteria (Burkholderiaceae, Eggerthellaceae and Erysipelotrichaceae) that encode larg...
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| Published in: | Nature microbiology Vol. 9; no. 1; pp. 55 - 69 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
London
Nature Publishing Group UK
01-01-2024
Nature Publishing Group |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Respiratory reductases enable microorganisms to use molecules present in anaerobic ecosystems as energy-generating respiratory electron acceptors. Here we identify three taxonomically distinct families of human gut bacteria (Burkholderiaceae, Eggerthellaceae and Erysipelotrichaceae) that encode large arsenals of tens to hundreds of respiratory-like reductases per genome. Screening species from each family (
Sutterella wadsworthensis
,
Eggerthella lenta
and
Holdemania filiformis
), we discover 22 metabolites used as respiratory electron acceptors in a species-specific manner. Identified reactions transform multiple classes of dietary- and host-derived metabolites, including bioactive molecules resveratrol and itaconate. Products of identified respiratory metabolisms highlight poorly characterized compounds, such as the itaconate-derived 2-methylsuccinate. Reductase substrate profiling defines enzyme–substrate pairs and reveals a complex picture of reductase evolution, providing evidence that reductases with specificities for related cinnamate substrates independently emerged at least four times. These studies thus establish an exceptionally versatile form of anaerobic respiration that directly links microbial energy metabolism to the gut metabolome.
Three distinct families of gut bacteria encode an unprecedented number of respiratory-like reductases per genome to perform anaerobic respiration of biomedically relevant substrates. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 A.S.L., E.G.P., and S.H.L. conceptualized the project. A.S.L., I.T.Y., P.N.B., J.S., K.S., and D.S. performed experiments. A.S.L. M.S.S., P.N.B., and S.H.L. analyzed data. A.S.L., I.T.Y., P.N.B., J.S., and K.S. performed growth assays. A.S.L. performed ATP determination assays. A.S.L. and J.S. performed protein expression and purification, and reductase activity assays. M.S.S., R.M., and A.M.E. performed bioinformatic analysis, including phylogeny and pangenomes. A.S.L., R.R., R.S., and A.S. performed bioinformatics analysis of transcriptomic data. M.W.M., W.L., D.M., M.M., A.M.S. performed and analyzed mass spectrometry. A.T.I. performed and analyzed proteomics data. A.S.L., P.N.B., J.S., and E.W. performed animal experiments and maintenance. M.A.O. provided human fecal samples for analysis. A.S.L. and S.H.L. wrote the manuscript. Author contributions |
| ISSN: | 2058-5276 2058-5276 |
| DOI: | 10.1038/s41564-023-01560-2 |