Abstract: The present invention relates to compounds and methods which may be useful as treatments of diseases.

Abstract: The present invention is related to production of a sterol mix in a modified yeast cell, wherein the amount of zymosterol present in said mix is dramatically reduced or abolished via modification of sterol acyltransferase activity within said yeast. The modified yeast cell can be used for production of vitamin D3 or derivatives and/or metabolites thereof.

Abstract: The present invention relates to Bacillus strains which improves health and performance of production animals. The invention further relates to compositions comprising the Bacillus strains.

Abstract: The disclosed embodiments concern index oligonucleotides configured to identify sources of samples of nucleic acids and methods, apparatus, systems and computer program products for identifying and making the index oligonucleotides. In some implementations, the index oligonucleotides include a set of index sequences, a Hamming distance between any two index sequences of the set of index sequences meeting one or more criteria. System, apparatus, and computer program products are also provided for determining a sequence of interest using the index oligonucleotides.

Abstract: The disclosed embodiments concern index oligonucleotides configured to identify sources of samples of nucleic acids and methods, apparatus, systems and computer program products for identifying and making the index oligonucleotides. In some implementations, the index oligonucleotides include a set of index sequences, a Hamming distance between any two index sequences of the set of index sequences meeting one or more criteria. System, apparatus, and computer program products are also provided for determining a sequence of interest using the index oligonucleotides.

Abstract: The present invention provides methods and compositions for tagging long fragments of a target nucleic acid for sequencing and analyzing the resulting sequence information in order to reduce errors and perform haplotype phasing, for example.

Abstract: The invention relates to novel biocatalytic processes comprising the whole cell reduction of dehydrocholic acid (DHCA) compounds, novel 7?-hydroxy steroid dehydrogenase mutants, the sequences coding for these enzyme mutants, methods for producing the enzyme mutants and use thereof in enzymatic conversions of cholic acid compounds, and in particular in the production of ursodesoxycholic acid (UDCA); also a subject of the invention are novel methods for the synthesis of UDCA using the enzyme mutants; and in particular a further improved method for producing UDCA using recombinant whole cell biocatalysts.

Abstract: The invention relates to an isolated, genetically modified, living non-mammal organism, having increased HMG-CoA-reductase activity compared to the wild type, and having reduced C24-methyltransferase and/or delta22-desaturase activity compared to the wild type. The invention is characterized in that the organism has increased dehydrocholesterol-delta70-reductase activity compared to the wild type. The invention further relates to different uses of such an organism, to a test kit comprising such an organism, and to a membrane extract of such an organism.

Abstract: The present invention provides methods, compositions and kits for using a transposase and a transposon end for generating extensive fragmentation and 5?-tagging of double-stranded target DNA in vitro, then using a DNA polymerase for generating 5?- and 3?-tagged single-stranded DNA fragments without performing a PCR amplification reaction, wherein the first tag on the 5?-ends exhibits the sequence of the transferred transposon end and optionally, an additional arbitrary sequence, and the second tag on the 3?-ends exhibits a different sequence from the sequence exhibited by the first tag. The method is useful for generating 5?- and 3?-tagged DNA fragments for use in a variety of processes, including processes for metagenomic analysis of DNA in environmental samples, copy number variation (CNV) analysis of DNA, and comparative genomic sequencing (CGS), including massively parallel DNA sequencing (so-called “next generation sequencing).

Abstract: This disclosure provides methods and compositions for tagging long fragments of a target nucleic acid for sequencing and analyzing the resulting sequence information in order to reduce errors and perform haplotype phasing, for example.

Abstract: A process for the enzymatic regeneration of the redox cofactors NAD+/NADH and NADP+/NADPH in a one-pot reaction, wherein, as a result of at least two further enzymatically catalyzed redox reactions proceeding in the same reaction batch (product-forming reactions), one of the two redox cofactors accumulates in its reduced form and, respectively, the other one in its oxidized form, characterized in that a) in the regeneration reaction which reconverts the reduced cofactor into its original oxidized form, oxygen or a compound of general formula R1C(O)COOH is reduced, and b) in the regeneration reaction which reconverts the oxidized cofactor into its original reduced form, a compound of general formula R2CH(OH)R3 is oxidized and wherein R1, R2 and R3 in the compounds have different meanings.

Abstract: The present invention provides compounds of Formula (I-A), (I-B), and (I-C), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting Myc (e.g., c-Myc) activity. The present invention further provides methods of using the compounds described herein for treating Myc-mediated disorders (e.g., cancer and other proliferative diseases). The present invention also provides assays for identifying Myc inhibitors.

Abstract: The present invention provides compounds of Formula (I-A), (I-B), and (I-C), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting Myc (e.g., c-Myc) activity. The present invention further provides methods of using the compounds described herein for treating Myc-mediated disorders (e.g., cancer and other proliferative diseases). The present invention also provides assays for identifying Myc inhibitors.

Abstract: This disclosure provides methods and compositions for tagging long fragments of a target nucleic acid for sequencing and analyzing the resulting sequence information in order to reduce errors and perform haplotype phasing, for example.

Abstract: The present invention provides methods, compositions and kits for using a transposase and a transposon end for generating extensive fragmentation and 5?-tagging of double-stranded target DNA in vitro, then using a DNA polymerase for generating 5?- and 3?-tagged single-stranded DNA fragments without performing a PCR amplification reaction, wherein the first tag on the 5?-ends exhibits the sequence of the transferred transposon end and optionally, an additional arbitrary sequence, and the second tag on the 3?-ends exhibits a different sequence from the sequence exhibited by the first tag. The method is useful for generating 5?- and 3?-tagged DNA fragments for use in a variety of processes, including processes for metagenomic analysis of DNA in environmental samples, copy number variation (CNV) analysis of DNA, and comparative genomic sequencing (CGS), including massively parallel DNA sequencing (so-called “next-generation sequencing.

Abstract: Methods and compositions are described for detecting hydroxymethylated nucleotides (hmNs) in a polynucleotide preparation with a view to mapping the location of hmNs in a genome, quantifying the occurrence of hmNs at selected loci and correlating the occurrence of hmNs with gene expression and phenotypic traits. Embodiments describe the use of modifying enzymes together with site-specific endonucleases to detect the hmNs.

Abstract: The invention relates to the production of glucuronic and glucaric acid in cells through recombinant expression of myo-inositol 1-phosphate synthase, myo-inositol oxygenase and uronate dehydrogenase. Cloning and characterization of the gene encoding uronate dehydrogenase is also disclosed.

Abstract: The invention provides 12?-hydroxysteroid dehydrogenases, nucleic acid sequences coding for the same, expression cassettes and vectors, recombinant microorganisms containing the corresponding coding nucleic acid sequences, methods for producing said 12?-hydroxysteroid dehydrogenases, methods for enzymatic oxidation of 12?-hydroxysteroids using said enzyme, methods for enzymatic reduction of 12-ketosteroids using said enzyme, methods for qualitative or quantitative determination of 12-ketosteroids and/or 12?-hydroxysteroids using said 12?-hydroxysteroid dehydrogenases and methods for production of ursodesoxycholic acid, comprising the enzyme-catalysed cholic acid oxidation using said 12?-hydroxysteroid dehydrogenases.

Abstract: The invention relates to novel 7?-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.

Abstract: The invention relates to novel 7?-hydroxysteroid dehydrogenases which are obtainable from bacteria of the genus Collinsella, especially of the strain Collinsella aerofaciens, to the sequences encoding said enzymes, to methods for producing said enzymes and to their use in the enzymatic conversion of cholic acid compounds, and especially in the production of ursodeoxycholic acid (UDCS). The invention also relates to novel methods for the synthesis UDCS.

Abstract: A method for enzymatic preparation of compounds of the general formula (2) from unsaturated alkene derivatives of the general formula (1) by reducing a compound of the formula (1) in the presence of a reductase, comprising at least one of the polypeptide sequences SEQ ID NO: 1, 2 or 3 or having a functionally equivalent polypeptide sequence which is at least 80% identical to SEQ ID NO: 1, 2 or 3.

Abstract: A process for the enantioselective reduction of compounds having a steroid structure (ABCD) including one or several heteroatoms, one or several double bonds and/or aromatic components in the ring structure and having at least one oxo group at positions 3, 7, 11, 12 or 17 in the steroid ring system or in the a-position of any carbon moiety of the steroid structure: comprising providing the oxosteroid compound in the reaction at a concentration of ?50 g/L, a reduced cofactor NADH or NADPH, a hydroxysteroid dehydrogenase and a secondary alcohol or cycloalknaol to effect the enantioselective reduction.

Abstract: We describe a PS4 variant polypeptide derivable from a parent polypeptide having non-maltogenic exoamylase activity, in which the PS4 variant polypeptide comprises an amino acid substitution at position 307 to lysine (K) or arginine (R), with reference to the position numbering of a Pseudomonas saccharophilia exoamylase sequence shown as SEQ ID NO: 1. Preferably, the PS4 variant polypeptide further comprises an amino acid substitution at position 70, preferably G70D. The amino acid at positions 272 and 303 of the sequence of the are preferably histidine (H) and glycine (G).

Abstract: The present invention embraces a fungal strain deficient in nicotinamide riboside import and salvage and use thereof for producing nicotinamide riboside. Methods for producing nicotinamide riboside and a nicotinamide riboside-supplemented food product using the strain of the invention are also provided.

Abstract: The invention relates to 12 ?-hydroxysteroid dehydrogenases, nucleic acid sequences coding for the same, expression cassettes and vectors, recombinant microorganisms containing the corresponding coding nucleic acid sequences, a method for producing said 12 ?-hydroxysteroid dehydrogenases, a method for enzymatic oxidation of 12 ?-hydroxysteroids using said enzyme, a method for enzymatic reduction of 12-ketosteroids using said enzyme, a method for qualitative or quantitative determination of 12-ketosteroids and/or 12?-hydroxysteroids using said 12?-hydroxysteroid dehydrogenases and a method for production of ursodesoxycholic acid, comprising the enzyme-catalysed cholic acid oxidation using said 12 ?-hydroxysteroid dehydrogenases.

Abstract: The invention relates to the direct selection of metabolic pathways having a determined function in the transformation of a substrate {Ai} into a target product {B}, which is of interest in the industrial, pharmaceutical or agri-food sectors. More specifically, the invention relates to the detection, within metagenomic libraries, of novel biosynthesis pathways involved in a biochemical reaction having a known product {B}. The selection and characterisation of said novel metabolic pathways enables {B} to be produced enzymatically. The invention provides an alternative to the chemical synthesis of the molecule in question {B}. Moreover, and above all, the invention can be used specifically to target and exploit the only metabolic pathways enabling the transformation of {Ai} into {B}, while eliminating the associated metabolic pathways that can catabolise the target product {B}.

Abstract: A process for the enantioselective enzymatic reduction of compounds which comprise a steroid structure (ABCD) including one or several heteroatoms, one or several double bonds and/or one aromatic component in the ring structure and have at least one oxo group at position 3, 7, 11, 12 or 17 in the steroid ring system or in the ?-position at any carbon moiety on the steroid skeleton (=oxosteroid compound), wherein the oxosteroid compound is reduced with a hydroxysteroid dehydrogenase in the presence of a cofactor NADH or NADPH, is characterized in that a) the oxosteroid compound is provided in the reaction at a concentration of ?50 g/l, b) the oxidized cofactor NAD or NADP formed by the hydroxysteroid dehydrogenase is regenerated continuously by oxidation of a secondary alcohol of general formula RXRYCHOH, wherein RX, RY independently represent hydrogen, a branched or unbranched C1-C8-alkyl and Ctotal?3, or by oxidation of a C4-C6-cycloalkanol, and c) an additional oxidoreductase/alcohol dehydrogenase is u

Abstract: Nucleotide sequences encoding formate dehydrogenases D & E and a method for preparing succinic acid using the same, more particularly, formate dehydrogenases D & E converting formate to carbon dioxide and hydrogen, fdhD and fdhE nucleotide sequences encoding the formate dehydrogenases D & E, recombinant vectors containing the nucleotide sequences, microorganisms transformed with the recombinant vectors, and a method for preparing succinic acid using the transformed microorganism.

Abstract: The present invention describes a novel recombinant NADH recycling system that is used as a process for producing reduced compounds. In a specific embodiment, the reduced compounds include ethanol, succinate, lactate, a vitamin, a pharmaceutical and a biodegraded organic molecule. The NADH recycling system effects metabolic flux of reductive pathways in aerobic and anaerobic environments.

Abstract: A microbe-specific medium for detection of vancomycin-resistant Enterococci in a test sample within 24 hours and preferably within 18 hours. The testing medium provides a selective growth medium for vancomycin-resistant Enterococci and includes specific nutrient indicators which only the target microbe can significantly metabolize and use for growth. The nutrient indicator contain a nutrient moiety and a detectable moiety linked together by a covalent bond. The nutrient indicators produce detectable signals only if the nutrient indicators are hydrolyzed by the Enterococci specific enzymes including ?-glucosidase and pyrrolidonyl arylamidase.

Abstract: The present invention is a novel process for the transformation of 17&agr;-hydroxy-6&agr;-methylpregn-4-ene-3,20-dione 17-acetate (I) to 11&bgr;,17&agr;,21-trihydroxy-6&agr;-methylpregna-1,4-diene-3,20-dione 21-acetate (VI)

Abstract: Reagents that regulate human 3-&bgr;-hydroxysteroid dehydrogenase-isomerase and reagents which bind to human 3-&bgr;-hydroxysteroid dehydrogenase-isomerase gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, cancer.

Abstract: A strain derived from Zymomonas mobilis ATCC31821 or its derivative capable of producing ethanol upon fermentation of a carbohydrate medium containing xylose to provide enhanced xylose utilization and enhanced ethanol process yield, the strain or its derivative comprising exogenous genes encoding xylose isornerase, xylulokinase, transaldolase and transketolase, the genes are fused to at least one promotor recognized by Zymomonas which regulates the expression of at least one of the genes.

Abstract: Efficient synthetic routes for the preparation of rhinovirus protease inhibitors of formula I, key intermediates useful in those synthetic routes, as well as a continuous membrane reactor useful for those synthetic routes. These compounds of formula I, as well as pharmaceutical compositions that contain these compounds, are suitable for treating patients or hosts infected with one or more picornaviruses.

Abstract: The present invention is a novel process for the transformation of 17&agr;-hydroxy-6&agr;-methylpregn-4-ene-3,20-dione 17-acetate (I) 1

Abstract: A microbe-specific medium for detection of vancomycin-resistant Enterococci in a test sample within 24 hours and preferably within 18 hours. The testing medium provides a selective growth medium for vancomycin-resistant Enterococci and includes specific nutrient indicators which only the target microbe can significantly metabolize and use for growth. The nutrient indicator contain a nutrient moiety and a detectable moiety linked together by a covalent bond. The nutrient indicators produce detectable signals only if the nutrient indicators are hydrolyzed by the Enterococci specific enzymes including &bgr;-glucosidase and pyrrolidonyl arylamidase.

Abstract: A microbe-specific medium for detection of vancomycin-resistant Enterococci in a test sample within 24 hours and preferably within 18 hours. The testing medium provides a selective growth medium for vancomycin-resistant Enterococci and includes specific nutrient indicators which only the target microbe can significantly metabolize and use for growth. The nutrient indicator contain a nutrient moiety and a detectable moiety linked together by a covalent bond. The nutrient indicators produce detectable signals only if the nutrient indicators are hydrolyzed by the Enterococci specific enzymes including &bgr;-glucosidase and pyrrolidonyl arylamidase.

Abstract: According to the present invention, a process for producing a practical cholesterol-reduced substance by converting cholesterol contained in foods and feeds to coprostanol having very low intestinal tract absorbability by utilizing enzymatic action is provided.

Abstract: The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

Abstract: Microorganisms from the genus Bacillus are used to convert chenodeoxycholic acid to 3-alpha-hydroxy-7-keto-5-beta-cholanic acid under aerobic conditions and alkaline pH. Preferred strains are Bacillus FERM BP-4390, Bacillus FERM BP-4391, Bacillus FERM BP-3651, Bacillus FERM BP-3393, Bacillus FERM BP-3398, Bacillus FERM BP-3395 and Bacillus FERM BP-3396. Microorganisms from the genus Bacillus are used to convert cholic acid to 3-alpha-hydroxy-7,12-diketo-5-beta-cholanic acid under aerobic conditions and alkaline pH. Preferred strains are Bacillus FERM BP-3393 and Bacillus FERM BP-3398. Microorganisms from the genus Bacillus are used to convert cholic acid to 3-alpha, 12-alpha-dihydroxy-7-keto-5-cholanic acid under aerobic conditions and alkaline PH. Preferred strains are Bacillus FERM BP-3395 and Bacillus FERM BP-4390.

Abstract: A process for the production of 17-oxosteroids by fermentative oxidation of 17.beta.-hydroxy steroids is described, which is characterized in that for the fermentation, a bacterial culture of the species Mycobacterium spec. NRRL B-3805, Mycobacterium spec. NRRL B-3683, Mycobacterium phlei NRRL B-8154 or Mycobacterium fortuitum NRRL B-8153 is used.

Abstract: 3-.alpha., 7-.alpha.-dihydroxy-12-keto-5-.beta.-cholanic acid is microbially produced from cholic acid by alkalophilic Bacillus strains. The preferred strains are Bacillus sp. FERM BP-3394 and Bacillus sp. FERM BP-3397.

Abstract: A process for the preparation of a compound of the formula ##STR1## wherein R.sub.1 is alkyl of 1 to 3 carbon atoms, R.sub.2 is alkyl of 1 to 12 carbon atoms, R.sub.3 is alkyl of 1 to 4 carbon atoms comprising reacting a compound of the formula ##STR2## wherein R.sub.4 is a remainder of an easily cleavable ether, K is a protected ketone function in the form of ketal, thioketal or mixed ketal and R.sub.1 has the above definition with a magnesium organic compound reagent of the formulaHalMg--CH.sub.2 --R.sub.2 Awherein Hal is a halogen and R.sub.2 is defined as above to obtain a compound of the formula ##STR3## wherein R.sub.1, R.sub.2 and K are defined as above, reacting the latter with an acylation agent to obtain a compound of the formula ##STR4## wherein R.sub.5 is alkyl of 1 to 6 carbon atoms or aryl of 6 to 10 carbon atoms and R.sub.1, R.sub.2 and K are defined as above, reacting the latter with an appropriate alkylation agent to obtain a compound of the formula ##STR5## wherein R.sub.1, R.sub.2, R.sub.

Abstract: A process for the production of 4-pregnene-3,20-dione and its derivatives of general formula I ##STR1## in which R.sub.1 means a hydrogen atom, a fluorine atom or a methyl group,R.sub.2 represents a hydrogen atom or a hydroxy group, andR.sub.3 and R.sub.4 together symbolize a carbon-carbon bond orR.sub.3 represents a hydrogen atom, a hydroxy group or an alkanoyloxy group with up to 6 carbon atoms andR.sub.4 means a hydrogen atom or a methyl group, is described, which is characterized in that a pregnane derivative of general formula II ##STR2## in which R.sub.1, R.sub.3 and R.sub.4 have the above-mentioned meaning, symbolizes a single bond or a double bond,R.sub.5 represents a hydrogen atom, a hydroxy group or an alkanoyloxy group with at most 6 carbon atoms andR.sub.6 means a hydrogen atom or an alkanoyl group with at most 6 carbon atoms, is fermented with a bacterial culture of species Mycobacterium spec. NRRL B-3805.

Abstract: The invention provides a novel process for the production of 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione which comprises culturing a microorganism belonging to the genus Myrothecium and capable of hydrolyzing 4-androstene-3,17-dione to produce 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione in a medium supplemented with 4-androstene-3,17-dione, and isolating 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione from the cultured medium. According to the process of the present invention, 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione and 14.alpha.-hydroxy-4-androstene-3,6,17-trione can be produced with a high yield in a simple manner.

Abstract: 9.alpha.-hydroxy-17-keto steroids are prepared by fermenting steroids having a C-17-side chain of 5-10 carbon atoms inclusive, with the novel Mycobacterium species CBS 482.86. Starting from various substrates containing a 5-10 C carbon chain on C-17, 9.alpha.-hydroxyandrost-4-ene-3,17-dione, 7.alpha.,9.alpha.,12.alpha.-trihydroxyandrost-4-ene-3,17-dione or 9.alpha.-hydroxyandrost-4,11-diene-3,17-dione is obtained in high yield. The resulting compounds are useful intermediates in the synthesis of therapeutically important steroids, particularly corticosteroids.

Abstract: A process is claimed for the preparation of 1-methyl-1,4-androstadiene-3,17-dione characterized by fermenting 1-methyl-5.alpha.-androst-1-ene-3,17-dione (metenolone) with a microorganism culture of the genera Nocardia, Mycobacterium, or Fusarium.

Abstract: The present invention involves processes for 1,2-dehydrogenation of .DELTA..sup.4 -3-keto C.sub.21 -hemiester steroids of formula (I) ##STR1## with Arthrobacter simplex or Bacterium cyclooxydans to produce the corresponding .DELTA..sup.1,4 -3-keto C.sub.21 hemiester of formula (II) ##STR2## or free alcohol thereof with improved yields. The advantage is that the processes utilize higher substrate concentrations and give shorter reaction times than previously were known.

Abstract: The present invention provides a process for the production of proteins or protein-containing gene products by transformation of eukaryotic host cells with a recombinant DNA molecule containing the gene for the desired protein, culturing the cells and isolating the gene product after expression, wherein, as host cells, there is used a yeast strain which is deficient in proteases A and B.

Abstract: Cells with an alteration at least in the gene involved in betaine catabolism, their preparation and their use, in particular for producing metabolites and/or enzymes, are disclosed.