An enzymatic pathway in the human gut microbiome that converts A to universal O type blood.
ABO Blood-Group System
/ immunology
Amidohydrolases
/ chemistry
Bacterial Proteins
/ chemistry
Blood Group Antigens
/ metabolism
Catalytic Domain
Clostridiales
/ enzymology
Crystallography, X-Ray
Erythrocytes
/ immunology
Feces
/ microbiology
Gastrointestinal Microbiome
Hexosaminidases
/ chemistry
Humans
Male
Metagenome
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
27
12
2018
accepted:
25
04
2019
pubmed:
12
6
2019
medline:
22
1
2020
entrez:
12
6
2019
Statut:
ppublish
Résumé
Access to efficient enzymes that can convert A and B type red blood cells to 'universal' donor O would greatly increase the supply of blood for transfusions. Here we report the functional metagenomic screening of the human gut microbiome for enzymes that can remove the cognate A and B type sugar antigens. Among the genes encoded in our library of 19,500 expressed fosmids bearing gut bacterial DNA, we identify an enzyme pair from the obligate anaerobe Flavonifractor plautii that work in concert to efficiently convert the A antigen to the H antigen of O type blood, via a galactosamine intermediate. The X-ray structure of the N-acetylgalactosamine deacetylase reveals the active site and mechanism of the founding member of an esterase family. The galactosaminidase expands activities within the CAZy family GH36. Their ability to completely convert A to O of the same rhesus type at very low enzyme concentrations in whole blood will simplify their incorporation into blood transfusion practice, broadening blood supply.
Identifiants
pubmed: 31182795
doi: 10.1038/s41564-019-0469-7
pii: 10.1038/s41564-019-0469-7
doi:
Substances chimiques
ABO Blood-Group System
0
Bacterial Proteins
0
Blood Group Antigens
0
Hexosaminidases
EC 3.2.1.-
Amidohydrolases
EC 3.5.-
acetylgalactosamine deacetylase
EC 3.5.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1475-1485Subventions
Organisme : CIHR
ID : MOP-136940
Pays : Canada
Organisme : NIGMS NIH HHS
ID : R24 GM098791
Pays : United States
Commentaires et corrections
Type : CommentIn
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