A prominent glycyl radical enzyme in human gut microbiomes metabolizestrans-4-hydroxy-l-proline.
The human microbiome encodes vast numbers of uncharacterized enzymes, limiting our functional understanding of this community and its effects on host health and disease. By incorporating information about enzymatic chemistry into quantitative metagenomics, we determined the abundance and distribution of individual members of the glycyl radical enzyme superfamily among the microbiomes of healthy humans. We identified many uncharacterized family members, including a universally distributed enzyme that enables commensal gut microbes and human pathogens to dehydratetrans-4-hydroxy-l-proline, the product of the most abundant human posttranslational modification. This "chemically guided functional profiling" workflow can therefore use ecological context to facilitate the discovery of enzymes in microbial communities.
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
B J
0000-0003-3220-9303
BJ
Levin
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
Y Y
0000-0003-1263-1515
YY
Huang
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
S C
0000-0002-1599-6635
SC
Peck
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Y
Y
Wei
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
A
A
Martínez-Del Campo
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
J A
JA
Marks
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.|Broad Institute, Cambridge, MA 02139, USA.
E A
EA
Franzosa
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.|Broad Institute, Cambridge, MA 02139, USA.
C
0000-0002-1110-0096
C
Huttenhower
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA. balskus@chemistry.harvard.edu.|Broad Institute, Cambridge, MA 02139, USA.
E P
0000-0001-5985-5714
EP
Balskus
D020816:Amino Acid Motifs; D000693:Anaerobiosis; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism*; D054892:Metagenome; D011394:Proline Oxidase / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011408:Propanediol Dehydratase / Q000737:chemistry / Q000235:genetics; D011499:Protein Processing, Post-Translational; D016415:Sequence Alignment
D011394:Proline Oxidase; D011408:Propanediol Dehydratase; D006909:Hydroxyproline