Xanthomonas maltophilia CBS 897.97 as a source of new 7β- and 7α-hydroxysteroid dehydrogenases and cholylglycine hydrolase: Improved biotransformations of bile acids

Pedrini, Paola; Andreotti, Elisa; Guerrini, Alessandra; Dean, Mariangela; Fantin, Giancarlo; Giovannini, Pier Paolo

doi:10.1016/j.steroids.2005.10.002

Cited by 44 publications

(37 citation statements)

References 28 publications

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“…Few enzymes (acylases, EC: 3.5.1) have been reported to hydrolyse glycinates and taurinates to the corresponding carboxylic acid. Recently, Pedrini et al [ 33 ] have isolated and characterized a cholylglycine hydrolase from Xanthomonas maltophilia CBS 827.97: this enzyme completely hydrolyses glycine and taurine conjugates in 20 minutes at 50 °C. Unfortunately the protein sequence of this enzyme is not reported, making recombinant expression and its industrial use impossible.…”

Section: Reviewmentioning

confidence: 99%

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

Tonin

Arends

2018

Beilstein J. Org. Chem.

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Ursodeoxycholic acid (UDCA) is a pharmaceutical ingredient widely used in clinics. As bile acid it solubilizes cholesterol gallstones and improves the liver function in case of cholestatic diseases. UDCA can be obtained from cholic acid (CA), which is the most abundant and least expensive bile acid available. The now available chemical routes for the obtainment of UDCA yield about 30% of final product. For these syntheses several protection and deprotection steps requiring toxic and dangerous reagents have to be performed, leading to the production of a series of waste products. In many cases the cholic acid itself first needs to be prepared from its taurinated and glycilated derivatives in the bile, thus adding to the complexity and multitude of steps involved of the synthetic process. For these reasons, several studies have been performed towards the development of microbial transformations or chemoenzymatic procedures for the synthesis of UDCA starting from CA or chenodeoxycholic acid (CDCA). This promising approach led several research groups to focus their attention on the development of biotransformations with non-pathogenic, easy-to-manage microorganisms, and their enzymes. In particular, the enzymatic reactions involved are selective hydrolysis, epimerization of the hydroxy functions (by oxidation and subsequent reduction) and the specific hydroxylation and dehydroxylation of suitable positions in the steroid rings. In this minireview, we critically analyze the state of the art of the production of UDCA by several chemical, chemoenzymatic and enzymatic routes reported, highlighting the bottlenecks of each production step. Particular attention is placed on the precursors availability as well as the substrate loading in the process. Potential new routes and recent developments are discussed, in particular on the employment of flow-reactors. The latter technology allows to develop processes with shorter reaction times and lower costs for the chemical and enzymatic reactions involved.

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Section: Reviewmentioning

confidence: 99%

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

Tonin

Arends

2018

Beilstein J. Org. Chem.

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“…Indeed the UDCA 3-azides were more toxic than the corresponding DCA compounds. The 7b-azido compound (34) was also cytotoxic (CC 50 99 lM) however the UDCA-based 24-azide had not effect on cell viability at 500 lM despite its high lipophilicity; (iv) the DCA and UDCA primary amides (25,14) markedly reduced viability (CC 50 39, 161 lM, respectively); (v) in contrast, the DCA methyl ester (24) was more toxic that DCA itself but the UDCA analogue 13 was not more toxic than UDCA. DCA methyl ester 24 was not acting as a prodrug for DCA in this context because it could be recovered unchanged from the medium at 24 h; (v) the 3-deoxy UDCA compound (17) was highly toxic; (vi) apart from the amide 14, the UDCA side chain analogs (18)(19)(20)(21)(22)(23) which are neutral and hydrophobic were not cytotoxic; (vii) oxidation of the steroid secondary alcohols to ketone level was associated with a reduction in cytotoxicity.…”

Section: Effects On Cell Viabilitymentioning

confidence: 99%

Bile acid toxicity structure–activity relationships: Correlations between cell viability and lipophilicity in a panel of new and known bile acids using an oesophageal cell line (HET-1A)

Sharma

Majer

Peta

et al. 2010

Bioorganic & Medicinal Chemistry

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“…The similar toxic impact of LCA was observed in C. sinensis newly excysted juveniles [13]. LCA is derived enzymatically from chenodeoxycholic acid and usually present in both human and bovine bile as a minor constituent [21-23]. Thus the worms were unable to tolerate LCA when it was present in higher concentrations (5-10 µM).…”

Section: Discussionmentioning

confidence: 73%

In Vitro Maintenance of Clonorchis sinensis Adult Worms

Uddin

Bae

et al. 2012

Korean J Parasitol

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Clonorchis sinensis is a biological carcinogen inducing human cholangiocarcinoma, and clonorchiasis is one of the important endemic infectious diseases in East Asia. The present study investigated survival longevity of C. sinensis adult worms in various in vitro conditions to find the best way of keeping the worms longer. The worms were maintained in 0.85% NaCl, 1×PBS, 1×Locke's solution, RPMI-1640, DMEM, and IMDM media, and in 1×Locke's solution with different supplements. All of the worms died within 3 and 7 days in 0.85% NaCl and 1×PBS, respectively, but survived up to 57 days in 1×Locke's solution. The worms lived for 106 days in DMEM, and 114 days in both RPMI-1640 and IMDM media. The survival rate in RPMI-1640 medium was the highest (50%) compared to that in DMEM (20±10%) and in IMDM (33.3±25.2%) after 3 months. The 1×Locke's solution with 0.005% bovine bile supplement showed increased duration of maximum survival from 42 days to 70 days. Higher concentration of bile supplements than 0.005% or addition of glucose were disadvantageous for the worm survival. The worms died rapidly in solutions containing L-aspartic acid, L-glutamic acid, and adenine compared to L-arginine, L-serine, and L-tryptophan. In conclusion, the 1×Locke's solution best supports the worms alive among inorganic solutions for 57 days, and the RPMI-1640 medium maintains living C. sinensis adults better and longer up to 114 days in vitro than other media.

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Xanthomonas maltophilia CBS 897.97 as a source of new 7β- and 7α-hydroxysteroid dehydrogenases and cholylglycine hydrolase: Improved biotransformations of bile acids

Cited by 44 publications

References 28 publications

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

Bile acid toxicity structure–activity relationships: Correlations between cell viability and lipophilicity in a panel of new and known bile acids using an oesophageal cell line (HET-1A)

In Vitro Maintenance of Clonorchis sinensis Adult Worms

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