Cyclohexane-1,2-dione hydrolase: A new tool to degrade alicyclic compounds

Fraas, Sonja; Steinbach, Alma K.; Tabbert, Anja; Harder, Jens; Ermler, Ulrich; Tittmann, Kai; Meyer, Axel; Kroneck, Peter M. H.

doi:10.1016/j.molcatb.2009.03.021

Cited by 25 publications

(21 citation statements)

References 7 publications

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“…An interesting compound in this context is cyclohexane-1,2-dione (11) because it has been successfully employed in the hydrolytic C À C bond ringcleavage reaction using ThDP-dependent flavoenzyme cyclohexane-1,2-dione hydrolase (CDH). [23] This reaction is completely different from the carboligation reaction discussed herein, and demonstrates the diversity of ThDP-dependent enzyme-catalyzed transformations.…”

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confidence: 74%

Enantioselective Intermolecular Aldehyde–Ketone Cross‐Coupling through an Enzymatic Carboligation Reaction

et al. 2010

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Thiamine diphosphate (ThDP)-dependent enzymes are wellestablished catalysts in the field of asymmetric synthesis. [1] One of the model reactions catalyzed by these enzymes is the asymmetric CÀC bond-formation reaction between two aldehyde substrates that leads to the formation of 2-hydroxyketones in high enantioselectivities. [2] Exchange of one of the aldehyde substrates in this reaction for a ketone [3] would offer the opportunity for the catalytic asymmetric formation of chiral tertiary alcohols, which are important structural units in natural products and bioactive agents. [4,5] During the last decade, different organocatalysts have been developed for the asymmetric aldehyde-ketone cross-coupling reaction, [6] and intramolecular variants of this reaction have been reported in the literature. [7,8] Most recently, Enders and Henseler described the direct intermolecular cross-coupling between aldehydes and trifluoromethyl ketones using a bicyclic triazolium salt as the catalyst. [9] The asymmetric intermolecular non-enzymatic coupling reaction with ketone acceptors should be more difficult, owing to the lower electrophilicity of the ketone carbonyl group, and the increased steric hindrance compared with aldehyde substrates, and has not yet been reported in the literature. Herein, we present an asymmetric intermolecular aldehyde-ketone carboligation reaction using a ThDP-dependent enzyme as the catalyst (Scheme 1).Branched-chain sugars are important bioactive carbohydrates and are widely represented in nature. Using feeding experiments, it can be shown that the two-carbon branch of several of these sugar derivatives is derived from pyruvate. In 1972, Grisebach and Schmid postulated the participation of ThDP in this carboligation reaction. [10] In the biosynthetic pathway of yersiniose A, a two-carbon branched-chain 3,6di(deoxy)hexose that is found in the O-antigen of Yersinia pseudotuberculosis O:VI, the ThDP-dependent flavoenzyme YerE catalyzes the decarboxylation of pyruvate and the transfer of the activated acetaldehyde onto the carbonyl function of CDP-3,6-di(deoxy)-4-keto-d-glucose (CDP = cytidine-5'-diphosphate). [11,12] The enzymatic activity of YerE was confirmed by incubation of the protein with the enzymatically prepared physiological substrate (starting from CDP-d-glucose). The isolated product CDP-4-aceto-3,6dideoxygalactose was confirmed by NMR spectroscopy.To analyze the substrate range of the enzyme, we amplified the gene yerE from the chromosomal DNA of Y. pseudotuberculosis O:VI using a polymerase chain reaction. The gene was cloned into the pQE-60 expression vector and the recombinant protein was produced in Escherichia coli BL21(DE3) cells. The overexpressed C-terminal His-tagged YerE protein was purified to homogeneity by affinity chromatography using an Ni-NTA purification system (see the Supporting Information).The amino acid sequence of YerE is similar to that of the large subunit of E. coli acetohydroxyacid synthases (EcAHAS) (31 % identity). AHAS successfully catalyzed the ThDP-dependent ...

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confidence: 74%

Enantioselective Intermolecular Aldehyde–Ketone Cross‐Coupling through an Enzymatic Carboligation Reaction

et al. 2010

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“…These reactions have been demonstrated with cyclic alkanes in bacteria, which were oxidized to alcohols, then ketones, followed by cleavage via 2-oxepanone formation, and finally to dicarboxylic acids (30-32). With γ-HBCD, it would also be reasonable to invoke β-oxidation/decarboxylation as a biological pathway that could yield shorter, volatile metabolites observed in the urine, such as tribromobutene (γ-M11; Table 2; Fig.…”

Section: Discussionmentioning

confidence: 98%

Novel and Distinct Metabolites Identified Following a Single Oral Dose of α- or γ-Hexabromocyclododecane in Mice

Hakk

Szabo

Huwe

et al. 2012

Environ. Sci. Technol.

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The metabolism of α- and γ-hexabromocyclododecane (HBCD) was investigated in adult C57BL/6 female mice. α- or γ-[14C]HBCD (3 mg/kg bw) was orally administered with subsequent urine and feces collection for 4 consecutive days; a separate group of mice were dosed and sacrificed 3 hours post-exposure to investigate tissue metabolite levels. Extractable and non-extractable HBCD metabolites were quantitated in liver, blood, fat, brain, bile, urine and feces and characterized by LC/MS (ESI-). Metabolites identified were distinct between the two stereoisomers. In mice exposed to α-HBCD, four hydroxylated metabolites were detected in fecal extracts, and one of these metabolite isomers was consistently characterized in liver, brain, and adipose tissue extracts. In contrast, mice exposed to γ-HBCD contained multiple isomers of monohydroxy-pentabromocyclododecene, dihydroxy-pentabromocyclododecene, and dihydroxy-pentabromocyclododecadiene in the feces while only a single monohydroxy-pentabromocyclododecane metabolite was measured in liver and adipose tissue. Both stereoisomers were transformed to metabolites which formed covalent bonds to proteins and/or lipids in the gut as evidenced by high fecal non-extractables. Although the potential toxicity of these free and bound metabolites remains to be determined, the presence of distinct metabolic products from the two main HBCD stereoisomers should allow biomarkers to be selected that may aid in characterizing sources of HBCD exposure.

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“…Among the enzymes that have been most intensively studied are transketolase (TK) from Escherichia coli and Saccharomyces cerevisiae , acetohydroxy acid synthase (AHAS) isoenzymes I–III from E. coli , benzoylformate decarboxylase (BFD) from Pseudomonas putida , benzaldehyde lyase (BAL) from Pseudomonas fluorescens , pyruvate decarboxylase (PDC) from S. cerevisiae , Zymomonas mobilis and Acetobacter pasteurianus , branched chain ketoacid decarboxylase from Lactococcus lactis , cyclohexane‐1,2‐dione hydrolase from Azoarcus sp. and 2‐succinyl‐5‐enolpyruvyl‐6‐hydroxy‐3‐cyclohexene‐1‐carboxylate (SEPHCHC) synthase (MenD) from E. coli . In addition to MenD, two further α‐ketoglutarate accepting enzymes were studied recently that represent the α‐ketoglutarate decarboxylase part of the α‐ketoglutarate dehydrogenase (KDH) complex and activity: SucA from E. coli and Kgd from Mycobacterium tuberculosis .…”

Section: Introductionmentioning

confidence: 99%

Engineering stereoselectivity of ThDP-dependent enzymes

Hailes

Rother

Müller

et al. 2013

FEBS J

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Thiamine diphosphate-dependent enzymes are broadly distributed in all organisms, and they catalyse a broad range of C-C bond forming and breaking reactions. Enzymes belonging to the structural families of decarboxylases and transketolases have been particularly well investigated concerning their substrate range, mechanism of stereoselective carboligation and carbolyase reaction. Both structurally different enzyme families differ also in stereoselectivity: enzymes from the decarboxylase family are predominantly R-selective, whereas those from the transketolase family are S-selective. In recent years a key focus of our studies has been on stereoselective benzoin condensation-like 1,2-additions. Meanwhile, several S-selective variants of pyruvate decarboxylase, benzoylformate decarboxylase and 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPH-CHC) synthase as well as R-selective transketolase variants were created that allow access to a broad range of enantiocomplementary a-hydroxyketones and a,a′-dihydroxyketones. This review covers recent studies and the mechanistic understanding of stereoselective C-C bond forming thiamine diphosphate-dependent enzymes, which has been guided by structure-function analyses based on mutagenesis studies and from influences of different substrates and organic co-solvents on stereoselectivity.

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Cyclohexane-1,2-dione hydrolase: A new tool to degrade alicyclic compounds

Cited by 25 publications

References 7 publications

Enantioselective Intermolecular Aldehyde–Ketone Cross‐Coupling through an Enzymatic Carboligation Reaction

Enantioselective Intermolecular Aldehyde–Ketone Cross‐Coupling through an Enzymatic Carboligation Reaction

Novel and Distinct Metabolites Identified Following a Single Oral Dose of α- or γ-Hexabromocyclododecane in Mice

Engineering stereoselectivity of ThDP-dependent enzymes

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