title: Clostridium scindens: a human gut microbe with a high potential to convert glucocorticoids into androgens.
abstract: Clostridium scindens American Type Culture Collection 35704 is capable of converting primary bile acids to toxic secondary bile acids, as well as converting glucocorticoids to androgens by side-chain cleavage. The molecular structure of the side-chain cleavage product of cortisol produced by C. scindens was determined to be 11β-hydroxyandrost-4-ene-3,17-dione (11β-OHA) by high-resolution mass spectrometry, (1)H and (13)C NMR spectroscopy, and X-ray crystallography. Using RNA-Seq technology, we identified a cortisol-inducible (≈ 1,000-fold) operon (desABCD) encoding at least one enzyme involved in anaerobic side-chain cleavage. The desC gene was cloned, overexpressed, purified, and found to encode a 20α-hydroxysteroid dehydrogenase (HSDH). This operon also encodes a putative "transketolase" (desAB) hypothesized to have steroid-17,20-desmolase/oxidase activity, and a possible corticosteroid transporter (desD). RNA-Seq data suggests that the two-carbon side chain of glucocorticords may feed into the pentose-phosphate pathway and are used as a carbon source. The 20α-HSDH is hypothesized to function as a metabolic "rheostat" controlling rates of side-chain cleavage. Phylogenetic analysis suggests this operon is rare in nature and the desC gene evolved from a gene encoding threonine dehydrogenase. The physiological effect of 11β-OHAD on the host or other gut microbes is currently unknown.
authors.affiliation: Department of Microbiology and Immunology and Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Ridlon
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ikegawa
authors.forename: João M P
authors.initials: JM
authors.lastname: Alves
authors.forename: Biao
authors.initials: B
authors.lastname: Zhou
authors.forename: Akiko
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Iida
authors.forename: Kuniko
authors.initials: K
authors.lastname: Mitamura
authors.forename: Genzoh
authors.initials: G
authors.lastname: Tanabe
authors.forename: Myrna
authors.initials: M
authors.lastname: Serrano
authors.forename: Ainee
authors.initials: A
authors.lastname: De Guzman
authors.forename: Patsy
authors.initials: P
authors.lastname: Cooper
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Buck
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Hylemon
mesh_terms: D000728:Androgens / Q000737:chemistry / Q000378:metabolism*; D000735:Androstenedione / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D003013:Clostridium / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism / Q000494:pharmacology; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D008958:Models, Molecular; D008968:Molecular Conformation; D009876:Operon / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism
chemical_list: D000728:Androgens; D005938:Glucocorticoids; D012333:RNA, Messenger; D000735:Androstenedione; C003582:11-hydroxyandrostenedione; D006913:Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D006854:Hydrocortisone
keywords: RNA-Seq; microbiome; steroid