Degussa Aktiengesellschaft

Pharmazell Gmbh

Forschungszentrum Juelich Gmbh

Other

Evonik Degussa Gmbh

Forschungszentrum Julich Gmbh

Kernforschungsanlage Julich

Gesellschaft Fur Biotechnologische Forschung Mbh (gbf)

Forschungszentrum J&uuml;lich Gmbh

Degussa Ag, Zweigniederlassung Wolfgang

Society for Biotechnical Research

Degussa Aktiengelleschaft

Gesellschaft Fur Biotechnologisch Forschung

Degussa Aktiengesellschaft and Gesellschaft Fur Biotechnologische

Evocatal Gmbh

Werner Hummel

Maria-Regina Kula

Daniel Bakonyi

Wolfgang Leuchtenberger

Horst Schutte

Bettina Riebel

Birgit Geueke

Karlheinz Drauz

Klaus Huthmacher

Christoph Weckbecker

Bettina Bommarius

Harald Groeger

Boqiao Sun

Christina Kantzow

Michael M&uuml;ller

Michael Wolberg

Christian Wandrey

Andreas Sebastian Bommarius

Thorsten Eggert

Helge Werner

Dirk Weuster-Botz

Arno Aigner

Michael Braun

Sven Bresch

Josef Altenbuchner

Steffen Osswald

Harald Gröger

Maria Regina Kula

Claudia Rollmann

Hendrik Hüsken

Andrea Weckbecker

Ralf Gross

Frank Boermann

Anne Menzel

Clemens Sambale

Udo Wendel

Peter Schadewaldt

Francoise Chamouleau

Chad Hagedorn

Kofi Abokitse

Karl-Erich JÄGER

Frank Rosenau

Andrea Seidel

Françoise Chamouleau

In various aspects and embodiments, the invention provides a nucleic acid molecule comprising a nucleotide sequence encoding a 7β-hydroxysteroid dehydrogenase (7β-HSDH) mutant that catalyzes at least the stereospecific enzymatic reduction of a 7-ketosteroid to the corresponding 7-hydroxysteroid, wherein the mutant has, compared to the wildtype 7β-HSDH of SEQ ID NO:2, a decreased substrate inhibition and/or an altered cofactor usage, and the mutant has, in comparison with the wildtype 7β-HSDH of SEQ ID NO:2, 1 to 15 amino acid additions, substitutions, deletions and/or inversions in the sequence motif VMVGRRE corresponding to positions 36 to 42 of SEQ ID NO:2.

7β-hydroxysteroid dehydrogenase mutants and process for the preparation of ursodeoxycholic acid

The present invention relates to a coupled biotransformation process of converting chenodeoxycholic acid (CDCA) and related compounds to ursodeoxycholic acid (UDCA) and related compounds. It also relates to the cloning, expression, and biochemical characterization of a novel NADP-dependent 7&#x3b1;-hydroxysteroid dehydrogenase (7&#x3b1;-HSDH) from, cofactor switch mutants thereof, and their application for the oxidation of bile acids. A further aspect of the invention relates to novel NADP-dependent cofactor switch mutants of the NADP-dependent 7&#x3b1;-HSDH ofand their application for the oxidation of bile acids.

Coupled, self-sufficient biotransformation of chenodeoxcholic acid to ursodeoxycholic acid and novel enzyme mutants applicable in said process

The invention provides novel 3&#x3b1;-hydroxysteroid dehydrogenase mutants, sequences that code for these enzyme mutants, methods for producing the enzyme mutants, and the use thereof in enzymatic reactions of cholic acid compounds, and in particular in the production of ursodeoxycholic acid (UDCA). The invention further provides processes for the synthesis of UDCA using the enzyme mutants and the production of UDCA using recombinant microorganisms that have been subjected to multiple modifications.

3&#x3b1;-hydroxysteroid dehydrogenase mutants and process for the preparation of ursodeoxycholic acid

One aspect of the invention provides a nucleic acid encoding a 7&#x3b2;-hydroxysteroid dehydrogenase (7&#x3b2;-HSDH) that catalyzes at least the stereospecific enzymatic reduction of a 7-ketosteroid to the corresponding 7-hydroxysteroid. The enzyme includes a mutation at position 64 of SEQ ID NO:2 or in the corresponding sequence positions of an amino acid sequence derived therefrom with at least 90% sequence identity to SEQ ID NO:2. The mutation at position 64 is the mutation R64X, wherein Xrepresents E, D, T, L, S, P, V, K, C, A, G, Q, F, W, I or Y. The enzyme shows the following property profile in comparison with the 7&#x3b2;-HSDH with SEQ ID NO:2: (a) an increased specific activity (Vmax [U/mg]) for NADPH in the enzymatic reduction of dehydrocholic acid (DHCA) with NADPH as cofactor.

7-beta-hydroxysteroid dehydrogenase mutants and process for the preparation of ursodeoxycholic acid

The invention relates to novel 7&#xdf;-hydroxysteroid dehydrogenase mutants, to the sequences which encode these enzyme mutants, to processes for the preparation of the enzyme mutants and to their use in enzymatic reactions of cholic acid compounds, in particular in the preparation of ursodeoxycholic acid (UDCS). The invention also relates to novel processes for the synthesis of UDCS using the enzyme mutants; and to the preparation of UDCS using recombinant, multiply-modified microorganisms.

7Beta-hydroxysteroid dehydrogenase mutants and process for the preparation of ursodeoxycholic acid

The invention relates to novel 7&#x3b2;-hydroxysteroid dehydrogenase mutants, to the sequences which code for these enzyme mutants, to processes for the preparation of the enzyme mutants and to their use in enzymatic conversions of cholic acid compounds, in particular in the preparation of ursodeoxycholic acid (UDCA); subject-matter of the invention is also novel processes for the synthesis of UDCA using enzyme mutants; and the preparation of UDCA using recombinant, multiply modified microorganisms.

7-&#x3b2;-hydroxysteroid dehydrogenase mutants and process for the preparation of ursodeoxycholic acid

The invention relates to novel 3-hydroxysteroid dehydrogenase mutants, to the sequences which code for these enzyme mutants, to processes for the preparation of the enzyme mutants and to their use in enzymatic conversions of cholic acid compounds, in particular in the preparation of ursodeoxycholic acid (UDCA); subject-matter of the invention is also novel processes for the synthesis of UDCA using enzyme mutants; and the preparation of UDCA using recombinant, multiply modified microorganisms.

3-alpha-hydroxysteroid dehydrogenase mutants and process for the preparation of ursodeoxycholic acid

The present invention relates to a process for preparing, in particular, enantiomerically enriched L-&#x3b1;-amino acids, in particular those of the general formula (I). In this connection, the process according to the invention uses 2-ketocarboxylic acids which are converted into the desired products using a whole-cell catalyst which comprises an amino acid dehydrogenase and a cofactor-regenerating enzyme. 

Process for preparing optically active amino acids using a whole-cell catalyst

The present application relates to a reaction system in which chemically valuable compounds can be obtained in high enantiomer concentrations with the aid of a coupled enzymatically operating transformation process. The coupled enzymatic reaction system comprises a cofactor-dependent enzymatic transformation of an organic compound and an enzymatic regeneration of the cofactor, wherein the reaction system operates in aqueous solution with an amount of substrate above the solubility limit thereof. In the preferred embodiments, an alcohol dehydrogenase is the cofactor-dependent enzyme, and the regeneration of the cofactor (e.g. NADH or NADPH) is acheved by means of formate dehydrogenase.

Coupled cofactor-dependent enzymatic reaction systems in aqueous media

The present invention is directed to a new NADH oxidase from, nucleic acids encoding the NADH oxidase, methods of producing the NADH oxidase, as well as there use in producing improved NADH oxidase enzymes and for producing chrial enantiomer-enriched organic compounds, such as alcohols and/or amino acids.

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The present invention relates to an alcohol dehydrogenase from. By means of such cofactor-dependent ADHs, chiral alcohols, which can be of use for use in organic syntheses, can advantageously be obtained with a cofactor-regenerating enzyme in a coupled enzymatic system. A nucleotide sequence, vehicles containing this, a polypeptide sequence and processes for mutation and use of the sequences are claimed.

The invention relates to recombinant microorganisms which, in comparison to the starting organism, have a higher concentration or activity of a D-amino acid oxidase, of an L-amino acid dehydrogenase, of an NADH cosubstrate regenerating enzyme and, if necessary, of a catalase. The invention also includes methods for preparing L-amino acids from D-amino acids using of these microorganisms.

Method for the preparation of L-amino acids from D-amino acids

The present invention is directed to a nucleotide sequence encoding D-amino oxidase (D-AAO, EC 1.4.3.3) fromThis may be inserted into an expression and used to transform a microbial host. The transformed microbial hosts ecomically produce D-AAO which may be used to oxidize D-amino acids.

The present invention is directed to a new NADH oxidase from Lactobacillus, nucleic acids encoding the NADH oxidase, methods of producing the NADH oxidase, as well as there use in producing improved NADH oxidase enzymes and for producing chrial enantiomer-enriched organic compounds, such as alcohols and/or amino acids.

NADH oxidase from lactobacillus

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Titz, Germany

Werner Hummel