Bile acids are the detergent molecules that solubilize dietary lipids and lipid-soluble vitamins. Humans synthesize bile acids with α-orientation hydroxyl groups that can be biotransformed by the gut microbiota to toxic, hydrophobic bile acids for instance deoxycholic acid (DCA). Gut microbiota also converts hydroxyl groups from the α-orientation through an oxo-intermediate to β-orientation, outcoming in more hydrophilic, less toxic bile acids. The interconversion is catalyzed by region- (C-3 vs. C-7) and stereospecific (α vs. β) hydroxysteroid dehydrogenases (HSDHs). Till now genes encoding the Urso- (7α-HSDH & 7β-HSDH) and iso- (3α- HSDH & 3β-HSDH) bile acid pathways were described. Lately, many human gut clostridia were examined to be encoded of 12α-HSDH, which interconverts DCA and 12-oxo lithocholic acid (12-oxoLCA). 12-HSDH will complete the epi-bile acid by converting it to the 12-oxoLCA to the 12-bile acid denoted epiDCA, yet a gene(s) encoding the enzyme is yet to be found. The 12-HSDH activity was confirmed in the culture of clostridium paraputrificum ATCC 25780. For six candidates C. paralutrificum ATCC 25780 oxidoreductase gene, it was found out that the first gene ( DR024_RS09610) encodes bile acid 12-HSDH. Phylogenetic examination showed unforeseen diversity for 12-HSDH, leading to the validation of two more bile acid 12-HSDHs through a synthetic biology approach. Comparing the prior phylogenetic analysis of 12-HSDH, researchers observed the first potential C-12 epimerization strains:  Collinsella tanakaei YIT 12063 and Collinsella stenosis DSM 13279. A Markov model search against the human gut metagenomes located putative 12- HSDH gene in around 30% of the subjects in the cohorts examined, showing the gene-related in the human gut microbiome. 

 

Link:www.tandfonline.com/doi/full/10.1080/19490976.2021.1907271