RRC ID 29357
Author Lee JY, Arai H, Nakamura Y, Fukiya S, Wada M, Yokota A.
Title Contribution of the 7β-hydroxysteroid dehydrogenase from Ruminococcus gnavus N53 to ursodeoxycholic acid formation in the human colon.
Journal J Lipid Res
Abstract Bile acid composition in the colon is determined by bile acid flow in the intestines, the population of bile acid-converting bacteria, and the properties of the responsible bacterial enzymes. Ursodeoxycholic acid (UDCA) is regarded as a chemopreventive beneficial bile acid due to its low hydrophobicity. However, it is a minor constituent of human bile acids. Here, we characterized an UDCA-producing bacterium, N53, isolated from human feces. 16S rDNA sequence analysis identified this isolate as Ruminococcus gnavus, a novel UDCA-producer. The forward reaction that produces UDCA from 7-oxo-lithocholic acid was observed to have a growth-dependent conversion rate of 90-100% after culture in GAM broth containing 1 mM 7-oxo-lithocholic acid, while the reverse reaction was undetectable. The gene encoding 7β-hydroxysteroid dehydrogenase (7β-HSDH), which facilitates the UDCA-producing reaction, was cloned and overexpressed in Escherichia coli. Characterization of the purified 7β-HSDH revealed that the kcat/Km value was about 55-fold higher for the forward reaction than for the reverse reaction, indicating that the enzyme favors the UDCA-producing reaction. As R. gnavus is a common, core bacterium of the human gut microbiota, these results suggest that this bacterium plays a pivotal role in UDCA formation in the colon.
Volume 54(11)
Pages 3062-9
Published 2013-11-1
DOI 10.1194/jlr.M039834
PII S0022-2275(20)35057-4
PMID 23729502
PMC PMC3793610
MeSH Amino Acid Sequence Bile Acids and Salts / metabolism Cloning, Molecular Colon / metabolism* Colon / microbiology Genome, Bacterial / genetics Humans Hydroxysteroid Dehydrogenases / chemistry Hydroxysteroid Dehydrogenases / genetics Hydroxysteroid Dehydrogenases / metabolism* Lithocholic Acid / analogs & derivatives Lithocholic Acid / metabolism Molecular Sequence Data Ruminococcus / enzymology* Ruminococcus / genetics Ursodeoxycholic Acid / metabolism*
IF 4.483
Times Cited 48
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
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The most frequently cited source Patent(IFI CLAIMS)
Total number of mentions 13
Altmetric score changes over past 6months 3.0
Resource
General Microbes JCM 6515 JCM 10188