One-step synthesis of 12-ketoursodeoxycholic acid from dehydrocholic acid using a multienzymatic system

  title={One-step synthesis of 12-ketoursodeoxycholic acid from dehydrocholic acid using a multienzymatic system},
  author={Luo Liu and Michael Braun and Gabi Gebhardt and Dirk Weuster‐Botz and Ralf Gross and Rolf D. Schmid},
  journal={Applied Microbiology and Biotechnology},
Abstract12-ketoursodeoxycholic acid (12-keto-UDCA) is a key intermediate for the synthesis of ursodeoxycholic acid (UDCA), an important therapeutic agent for non-surgical treatment of human cholesterol gallstones and various liver diseases. The goal of this study is to develop a new enzymatic route for the synthesis 12-keto-UDCA based on a combination of NADPH-dependent 7β-hydroxysteroid dehydrogenase (7β-HSDH, EC and NADH-dependent 3α-hydroxysteroid dehydrogenase (3α-HSDH, EC 1.1.1… 
Two-step enzymatic synthesis of ursodeoxycholic acid with a new 7β-hydroxysteroid dehydrogenase from Ruminococcus torques
Abstract 7β-Hydroxysteroid dehydrogenase (7β-HSDH) is a key enzyme for the efficient biosynthesis of ursodeoxycholic acid (UDCA), an effective pharmaceutical for primary biliary cirrhosis and human
Clean Enzymatic Oxidation of 12α‐Hydroxysteroids to 12‐Oxo‐Derivatives Catalyzed by Hydroxysteroid Dehydrogenase
The C12 specific oxidation of hydroxysteroids is an essential reaction required for the preparation of pharmaceutical ingredients like ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA),
Enzymatic routes for the synthesis of ursodeoxycholic acid.
Ursodeoxycholic acid, a secondary bile acid, is used as a drug for the treatment of various liver diseases, the optimal dose comprises the range of 8-10mg/kg/day. For industrial syntheses, the
Preparation of ursodeoxycholic acid from 7-ketone lithocholic acid by stereoselective electroreduction
BackgroundUrsodeoxycholic acid (UDCA) is an important clinical drug in the treatment of liver disease. In previous work, ursodeoxycholic acid was prepared by traditional organic synthesis. The
Dynamic mechanistic modeling of the multienzymatic one‐pot reduction of dehydrocholic acid to 12‐keto ursodeoxycholic acid with competing substrates and cofactors
A dynamic mechanistic model of this one‐pot reduction which involves three enzymes, four different bile acids, and two different cofactors, each with different oxidation states is presented.
Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review
This minireview 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.
Rapidly directional biotransformation of tauroursodeoxycholic acid through engineered Escherichia coli
This study reports the biotransformation of tauroursodeoxycholic acid (TUDCA) through Escherichia coli engineered with a two-step mimic biosynthetic pathway of TUDCA from taurochenode Oxycholic Acid (TCDCA), providing a potential approach for bear bile substitute production from cheap and readily available chicken bile.
Enzymatic cascade biosynthesis reaction of musky macrolactones from fatty acids.
The results reveal that the musky macrolactones, exaltolide and silvanone supra, could be synthesized in the hydroxylation-lactonization cascade reaction.
Large-scale production of tauroursodeoxycholic acid products through fermentation optimization of engineered Escherichia coli cell factory
This study provided a practical and environment friendly industrialized process for producing artificial substitute of bear bile powder from cheap and readily available chicken bile Powder using engineered E. coli microbial cell factory and put forward an interesting deep-tank static process to promote the enzyme-catalyzing reactions toward target compounds in synthetic biology-based fermentation.
Switching the substrate specificity from NADH to NADPH by a single mutation of NADH oxidase from Lactobacillus rhamnosus.
This work provides an efficient method for converting NAD(P)H specificity and shows that L179S mutant is a potential and efficient auxiliary enzyme for NADP+ regeneration.


Enzymatic reduction of dehydrocholic acid to 12-ketochenodeoxycholic acid with NADH regeneration
Abstract 12-Ketochenodeoxycholic acid, an essential intermediate in the synthesis of chenodeoxycholic acid, has been enzymatically prepared from dehydrocholic acid. The specific reduction of
A new enzymatic route to the synthesis of 12-ketoursodeoxycholic acid
SummaryCholic acid (3α,7α,12α-trihydroxy-5β-cholanoic acid) was completely and selectively transformed into 12-ketoursodeoxycholic acid (3α,7β-dihydroxy-12-oxo-5β-cholanoic acid) by means of two
The enzymic and chemical synthesis of ursodeoxycholic and chenodeoxycholic acid from cholic acid.
The third method proved the most successful giving an overall yield of 37% (UDC) whose structure was verified by mass spectroscopy of the methyl ester.
One-Pot Multienzymatic Synthesis of 12-Ketoursodeoxycholic Acid: Subtle Cofactor Specificities Rule the Reaction Equilibria of Five Biocatalysts Working in a Row
Received: November 21, 2008; Published online: March 17, 2009Dedicated to Prof. Karl “Kalle” Hult on the occasion of his 65th birthday.Abstract: The hydroxysteroid dehydrogenases(HSDHs)-catalyzed
Regio- and stereoselective reductions of dehydrocholic acid
A number of different chemical reductions were carried out on DHCA; among them hydrogenation with Raney Nickel in water under high-intensity ultrasound proved highly regio- and stereoselective, yielding 7,12-diketolithocolic acid exclusively.
Exploitation of the alcohol dehydrogenase-acetone NADP-regeneration system for the enzymatic preparative-scale production of 12-ketochenodeoxycholic acid.
The performance of a new NADP-regeneration system, based on the use of alcohol dehydrogenase (ADH)-acetone, has been investigated for the regioselective oxidation of cholic acid (1) to
Molecular Cloning, Overexpression, and Characterization of Steroid-inducible 3α-Hydroxysteroid Dehydrogenase/Carbonyl Reductase from Comamonas testosteroni
Results suggest that inducible 3α-HSD/CR from C. testosteroni is a novel member of the SDR superfamily, and its activity was determined for steroid and nonsteroidal carbonyl substrates.
12α‐Hydroxysteroid dehydrogenase from Clostridium group P, strain C 48–50
NADP(H)-dependent 12α-hydroxysteroid dehydrogenase (HSDH) from Clostridium group P, strain C 48–50, is still expressed at unusual high level (approximately 1% of total protein) under cultivation
Identification, cloning, heterologous expression, and characterization of a NADPH-dependent 7β-hydroxysteroid dehydrogenase from Collinsella aerofaciens
A gene encoding an NADPH-dependent 7β-hydroxysteroid dehydrogenase (7β-HSDH) from Collinsella aerofaciens DSM 3979 was identified and cloned and sequence comparison of the translated amino acid sequence suggests that the enzyme belongs to the short-chain dehydrogen enzyme superfamily.
7α-hydroxysteroid dehydrogenase from Escherichia coli B: Preliminary studies
Abstract 7α-Hydroxysteroid dehydrogenase was examined in crude preparations of one strain of Escherichia coli B which was devoid of both 3α- and 12α-dehydrogenase activities as shown by substrate