A patchwork pathway for oxygenase‐independent degradation of side chain containing steroids

The denitrifying betaproteobacterium Sterolibacterium denitrificans serves as model organism for studying the oxygen-independent degradation of cholesterol. Here, we demonstrate its capability of degrading various globally abundant side chain containing zoo-, phyto- and mycosterols. We provide the complete genome that empowered an integrated genomics/proteomics/metabolomics approach, accompanied by the characterization of a characteristic enzyme of steroid side chain degradation. The results indicate that individual molybdopterin-containing steroid dehydrogenases are involved in C25-hydroxylations of steroids with different isoprenoid side chains, followed by the unusual conversion to C26-oic acids. Side chain degradation to androsta-1,4-diene-3,17-dione (ADD) via aldolytic C-C bond cleavages involves acyl-CoA synthetases/dehydrogenases specific for the respective 26-, 24- and 22-oic acids/-oyl-CoAs and promiscuous MaoC-like enoyl-CoA hydratases, aldolases and aldehyde dehydrogenases. Degradation of rings A and B depends on gene products uniquely found in anaerobic steroid degraders, which after hydrolytic cleavage of ring A, again involves CoA-ester intermediates. The degradation of the remaining CD rings via hydrolytic cleavage appears to be highly similar in aerobic and anaerobic bacteria. Anaerobic cholesterol degradation employs a composite repertoire of more than 40 genes partially known from aerobic degradation in gammaproteobacteria/actinobacteria, supplemented by unique genes that are required to circumvent oxygenase-dependent reactions.

• Publication year

  2017

• Venue

  Environmental Microbiology

• Publication date

  2017-11-01

• Fields of study

  Biology, Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1111/1462-2920.13933PMID 28940833
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Catabolism of the Last Two Steroid Rings in Mycobacterium tuberculosis and Other Bacteria

  2017cited by this paper
• Sources, mechanisms, and fate of steroid estrogens in wastewater treatment plants: a mini review

  2017cited by this paper
• MicroScope in 2017: an expanding and evolving integrated resource for community expertise of microbial genomes

  2016cited by this paper
• Occurrence and removal of organic micropollutants: An overview of the watch list of EU Decision 2015/495.

  2016cited by this paper
• Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection.

  2016cited by this paper
• 25-Hydroxyvitamin D3 Synthesis by Enzymatic Steroid Side-Chain Hydroxylation with Water.

  2016cited by this paper
• Integrated multi-omics analyses reveal the biochemical mechanisms and phylogenetic relevance of anaerobic androgen biodegradation in the environment

  2015cited by this paper
• Unraveling Cholesterol Catabolism in Mycobacterium tuberculosis: ChsE4-ChsE5 α2β2 Acyl-CoA Dehydrogenase Initiates β-Oxidation of 3-Oxo-cholest-4-en-26-oyl CoA

  2015cited by this paper
• Functional analyses of three acyl-CoA synthetases involved in bile acid degradation in Pseudomonas putida DOC21.

  2015cited by this paper
• CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes

  2015cited by this paper
• Structural basis of enzymatic benzene ring reduction.

  2015cited by this paper
• Anoxic Androgen Degradation by the Denitrifying Bacterium Sterolibacterium denitrificans via the 2,3-seco Pathway

  2014cited by this paper
• Pathogen roid rage: Cholesterol utilization by Mycobacterium tuberculosis

  2014cited by this paper
• A Distinct MaoC-like Enoyl-CoA Hydratase Architecture Mediates Cholesterol Catabolism in Mycobacterium tuberculosis

  2014cited by this paper
• Evidence of distinct pathways for bacterial degradation of the steroid compound cholate suggests the potential for metabolic interactions by interspecies cross-feeding.

  2014cited by this paper
• Substrate Uptake and Subcellular Compartmentation of Anoxic Cholesterol Catabolism in Sterolibacterium denitrificans*

  2014cited by this paper
• An Oxygenase-Independent Cholesterol Catabolic Pathway Operates under Oxic Conditions

  2013cited by this paper
• FadD3 is an acyl‐CoA synthetase that initiates catabolism of cholesterol rings C and D in actinobacteria

  2013cited by this paper
• Genome Sequence of Pseudomonas sp. Strain Chol1, a Model Organism for the Degradation of Bile Salts and Other Steroid Compounds

  2013cited by this paper
• Nontargeted profiling of coenzyme A thioesters in biological samples by tandem mass spectrometry.

  2013cited by this paper
• The Essential Function of Genes for a Hydratase and an Aldehyde Dehydrogenase for Growth of Pseudomonas sp. Strain Chol1 with the Steroid Compound Cholate Indicates an Aldolytic Reaction Step for Deacetylation of the Side Chain

  2013cited by this paper
• Steroid degradation in Comamonas testosteroni.

  2012cited by this paper
• SOAPdenovo2: an empirically improved memory-efficient short-read de novo assembler

  2012cited by this paper
• Molecular characterization of three 3-ketosteroid-Δ(1)-dehydrogenase isoenzymes of Rhodococcus ruber strain Chol-4.

  2012cited by this paper
• Microbial steroid transformations: current state and prospects

  2012cited by this paper
• Molybdoenzyme That Catalyzes the Anaerobic Hydroxylation of a Tertiary Carbon Atom in the Side Chain of Cholesterol*

  2012cited by this paper
• Gene Cluster Encoding Cholate Catabolism in Rhodococcus spp

  2012cited by this paper
• Catabolism and biotechnological applications of cholesterol degrading bacteria

  2012cited by this paper
• Biosynthesis of cholesterol and other sterols.

  2011cited by this paper
• A Novel Testosterone Catabolic Pathway in Bacteria

  2011cited by this paper
• Sterol regulation of metabolism, homeostasis, and development.

  2011cited by this paper
• Adventures in Rhodococcus - from steroids to explosives.

  2011cited by this paper
• Biosynthesis of Cholesterol and Other Sterols

  2011cited by this paper
• Synthesis and biological activity of the (25R)-cholesten-26-oic acids--ligands for the hormonal receptor DAF-12 in Caenorhabditis elegans.

  2009cited by this paper
• Cholesterol oxidase: biochemistry and structural features

  2009cited by this paper
• Discovery and characterization of a new bacterial candidate division by an anaerobic sludge digester metagenomic approach

  2008cited by this paper
• Sterols and membrane dynamics

  2008cited by this paper
• A gene cluster encoding cholesterol catabolism in a soil actinomycete provides insight into Mycobacterium tuberculosis survival in macrophages

  2007cited by this paper
• Cholest-4-En-3-One-Δ1-Dehydrogenase, a Flavoprotein Catalyzing the Second Step in Anoxic Cholesterol Metabolism

  2007cited by this paper
• Study of Anoxic and Oxic Cholesterol Metabolism by Sterolibacterium denitrificans

  2007cited by this paper
• Initial Steps in the Anoxic Metabolism of Cholesterol by the Denitrifying Sterolibacterium denitrificans*♦

  2007cited by this paper
• Measurement of bile acid CoA esters by high-performance liquid chromatography-electrospray ionisation tandem mass spectrometry (HPLC-ESI-MS/MS).

  2005cited by this paper
• Syntons, metabolons and interactons: an exact graph-theoretical approach for exploring neighbourhood between genomic and functional data

  2005cited by this paper
• Structure of a xanthine oxidase-related 4-hydroxybenzoyl-CoA reductase with an additional [4Fe-4S] cluster and an inverted electron flow.

  2004cited by this paper
• Sterolibacterium denitrificans gen. nov., sp. nov., a novel cholesterol-oxidizing, denitrifying member of the beta-Proteobacteria.

  2003cited by this paper
• A New Bacterial Steroid Degradation Gene Cluster in Comamonas testosteroni TA441 Which Consists of Aromatic-Compound Degradation Genes for Seco-Steroids and 3-Ketosteroid Dehydrogenase Genes

  2003cited by this paper
• Synthesis of (25R)-26-hydroxycholesterol.

  2002cited by this paper
• Biotransformation of monoterpenes, bile acids, and other isoprenoids in anaerobic ecosystems.

  1998cited by this paper
• The mononuclear molybdenum enzymes.

  1996cited by this paper

• Ring A Cleaving Beta‐Diketone Hydrolase Is a Key Enzyme of Steroid Degradation in Anaerobic Bacteria

  2025cites this paper
• Harnessing and Degradation Mechanism of Persistent Polyethylene Waste by Newly Isolated Bacteria from Waxworm and Termite Gut Symbionts

  2025cites this paper
• Sad from Proteobacteria is a Structurally Distinct ALDH3 Enzyme Specialized for the Oxidation of Steroidal Aldehydes.

  2025cites this paper
• 7β-Hydroxysteroid dehydratase Hsh3 eliminates the 7-hydroxy group of the bile salt ursodeoxycholate during degradation by Sphingobium sp. strain Chol11 and other Sphingomonadaceae

  2025cites this paper
• Highly selective whole-cell 25-hydroxyvitamin D3 synthesis using molybdenum-dependent C25-steroid dehydrogenase and cyclodextrin recycling

  2024cites this paper
• Shy is a proteobacterial steroid hydratase which catalyzes steroid side chain degradation without requiring a catalytically inert partner domain

  2024cites this paper
• Bacterial stigmasterol degradation involving radical flavin delta-24 desaturase and molybdenum-dependent C26 hydroxylase

  2024cites this paper
• Detoxification of fluoroglucocorticoid by Acinetobacter pittii C3 via a novel defluorination pathway with hydrolysis, oxidation and reduction: Performance, genomic characteristics, and mechanism.

  2023cites this paper
• Genes and enzymes involved in the biodegradation of the quaternary carbon compound pivalate in the denitrifying Thauera humireducens strain PIV-1.

  2022cites this paper
• Biogas digestate as a sustainable phytosterol source for biotechnological cascade valorization

  2022cites this paper
• Structures and molecular mechanisms of action of the cholesterol C17 side-chain-degrading enzymes

  2022cites this paper
• Comparative Analysis of Bile-Salt Degradation in Sphingobium sp. Strain Chol11 and Pseudomonas stutzeri Strain Chol1 Reveals Functional Diversity of Proteobacterial Steroid Degradation Enzymes and Suggests a Novel Pathway for Side Chain Degradation

  2021cites this paper
• A fully reversible 25-hydroxy steroid kinase involved in oxygen-independent cholesterol side-chain oxidation

  2021cites this paper
• Degradation of Bile Acids by Soil and Water Bacteria

  2021influential citation
• Structural Basis of Cyclic 1,3‐Diene Forming Acyl‐Coenzyme A Dehydrogenases

  2021cites this paper
• Mycolicibacterium cell factory for the production of steroid-based drug intermediates.

  2021cites this paper
• ATP-dependent hydroxylation of an unactivated primary carbon with water

  2020cites this paper
• Channeling C1 Metabolism toward S-Adenosylmethionine-Dependent Conversion of Estrogens to Androgens in Estrogen-Degrading Bacteria

  2020cites this paper
• Steroids as Environmental Compounds Recalcitrant to Degradation: Genetic Mechanisms of Bacterial Biodegradation Pathways

  2019influential citation
• Retroconversion of estrogens into androgens by bacteria via a cobalamin-mediated methylation

  2019cites this paper
• Genome analysis of the steroid-degrading denitrifying Denitratisoma oestradiolicum DSM 16959 and Denitratisoma sp. strain DHT3

  2019influential citation
• Steroids originating from bacterial bile acid degradation affect Caenorhabditis elegans and indicate potential risks for the fauna of manured soils

  2019cites this paper
• Enzymes involved in phthalate degradation in sulphate-reducing bacteria.

  2019cites this paper
• The 7&agr;‐hydroxysteroid dehydratase Hsh2 is essential for anaerobic degradation of the steroid skeleton of 7&agr;‐hydroxyl bile salts in the novel denitrifying bacterium Azoarcus sp. strain Aa7

  2019cites this paper
• Microbial degradation of steroid sex hormones: implications for environmental and ecological studies

  2019influential citation
• Functional Characterization of Three Specific Acyl-Coenzyme A Synthetases Involved in Anaerobic Cholesterol Degradation in Sterolibacterium denitrificans Chol1S

  2018influential citation
• Bacterial steroid hydroxylases: enzyme classes, their functions and comparison of their catalytic mechanisms

  2018cites this paper
• Four Molybdenum-Dependent Steroid C-25 Hydroxylases: Heterologous Overproduction, Role in Steroid Degradation, and Application for 25-Hydroxyvitamin D3 Synthesis

  2018cites this paper
• Metabolites Involved in Aerobic Degradation of the A and B Rings of Estrogen

  2018influential citation
• Microbial Functional Responses to Cholesterol Catabolism in Denitrifying Sludge

  2018influential citation
• Identification of metabolites involved in the aerobic degradation of 1 estrogen A/B-rings

  2018influential citation
• Metagenomes Reveal Global Distribution of Bacterial Steroid Catabolism in Natural, Engineered, and Host Environments

  2018cites this paper