title: Identification of bypass reactions leading to the formation of one central steroid degradation intermediate in metabolism of different bile salts in Pseudomonas sp. strain Chol1.
abstract: The bile salts cholate, deoxycholate, chenodeoxycholate and lithocholate are released from vertebrates into soil and water where environmental bacteria degrade these widespread steroid compounds. It was investigated whether different enzymes are required for the degradation of these tri-, di- and monohydroxylated bile salts in the model organism Pseudomonas sp. strain Chol1. Experiments with available and novel mutants showed that the degradation of the C5-carboxylic side chain attached to the steroid skeleton is catalysed by the same set of enzymes. A difference was found for the degradation of partially degraded bile salts consisting of H-methylhexahydroindanone-propanoates (HIPs). With deoxycholate and lithocholate, which lack a hydroxy group at C7 of the steroid skeleton, an additional acyl-coenzyme A (CoA) dehydrogenase was required for β-oxidation of the C3-carboxylic side chain attached to the methylhexahydroindanone moiety. The β-oxidation of this side chain could be measured in vitro. With cholate and deoxycholate, a reductive dehydroxylation of the C12-hydroxy group of HIP was required. Deletion of candidate genes for this reaction step revealed that a so-far unknown steroid dehydratase and a steroid oxidoreductase were responsible for this CoA-dependent reaction. These results showed that all bile salts are channelled into a common pathway via bypass reactions with 3'-hydroxy-HIP-CoA as central intermediate.
authors.affiliation: Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität Münster, Corrensstr. 3, Münster, 48149, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Holert
authors.affiliation: Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität Münster, Corrensstr. 3, Münster, 48149, Germany.
authors.forename: Onur
authors.initials: O
authors.lastname: Yücel
authors.affiliation: Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität Münster, Corrensstr. 3, Münster, 48149, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Jagmann
authors.affiliation: Fachbereich Chemie, Universität Konstanz, Konstanz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Prestel
authors.affiliation: Fachbereich Chemie, Universität Potsdam, Potsdam, Germany.
authors.forename: Heiko M
authors.initials: HM
authors.lastname: Möller
authors.affiliation: Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität Münster, Corrensstr. 3, Münster, 48149, Germany. bodo.philipp@uni-muenster.de.
authors.forename: Bodo
authors.initials: B
authors.lastname: Philipp
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D020355:Cholates / Q000378:metabolism; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D011549:Pseudomonas / Q000235:genetics / Q000378:metabolism*; D013256:Steroids / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D020355:Cholates; D013256:Steroids; D006836:Hydro-Lyases