title: An unexplored pathway for degradation of cholate requires a 7α-hydroxysteroid dehydratase and contributes to a broad metabolic repertoire for the utilization of bile salts in Novosphingobium sp. strain Chol11.
abstract: Bile salts such as cholate are surface-active steroid compounds with functions for digestion and signaling in vertebrates. Upon excretion into soil and water bile salts are an electron- and carbon-rich growth substrate for environmental bacteria. Degradation of bile salts proceeds via intermediates with a 3-keto-Δ1,4-diene structure of the steroid skeleton as shown for e.g. Pseudomonas spp. Recently, we isolated bacteria degrading cholate via intermediates with a 3-keto-7-deoxy-Δ4,6-structure of the steroid skeleton suggesting the existence of a second pathway for cholate degradation. This potential new pathway was investigated with Novosphingobium sp. strain Chol11. A 7α-hydroxysteroid dehydratase encoded by hsh2 was identified, which was required for the formation of 3-keto-7-deoxy-Δ4,6-metabolites. A hsh2 deletion mutant could still grow with cholate but showed impaired growth. Cholate degradation of this mutant proceeded via 3-keto-Δ1,4-diene metabolites. Heterologous expression of Hsh2 in the bile salt-degrading Pseudomonas sp. strain Chol1 led to the formation of a dead-end steroid with a 3-keto-7-deoxy-Δ4,6-diene structure. Hsh2 is the first steroid dehydratase with an important function in a metabolic pathway of bacteria that use bile salts as growth substrates. This pathway contributes to a broad metabolic repertoire of Novosphingobium strain Chol11 that may be advantageous in competition with other bile salt-degrading bacteria.
authors.affiliation: Westfälische Wilhelms-Universität Münster Institut für Molekulare Mikrobiologie und Biotechnologie, Münster, 48149, Germany.
authors.forename: Onur
authors.initials: O
authors.lastname: Yücel
authors.affiliation: Westfälische Wilhelms-Universität Münster Institut für Molekulare Mikrobiologie und Biotechnologie, Münster, 48149, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Drees
authors.affiliation: Westfälische Wilhelms-Universität Münster Institut für Molekulare Mikrobiologie und Biotechnologie, Münster, 48149, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Jagmann
authors.affiliation: Centrum für Biotechnologie - CeBiTec, Universität Bielefeld, Bielefeld, 33501, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Patschkowski
authors.affiliation: Westfälische Wilhelms-Universität Münster Institut für Molekulare Mikrobiologie und Biotechnologie, Münster, 48149, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Philipp
mesh_terms: D020561:Alphaproteobacteria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001419:Bacteria / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D001673:Biodegradation, Environmental; D020355:Cholates / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D006914:Hydroxysteroids / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D011549:Pseudomonas / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D020355:Cholates; D006914:Hydroxysteroids; D006913:Hydroxysteroid Dehydrogenases