Abstract: A method for microbial production of epoxides and other oxygenated products is disclosed. The method uses a biocatalyst of methanotrophic bacteria cultured in a biphasic medium containing a major amount of a non-aqueous polar solvent. Regeneration of reducing equivalents is carried out by using endogenous hydrogenase activity together with supplied hydrogen gas. This method is especially effective with gaseous substrates and cofactors that result in liquid products.

Abstract: Methods for obtaining taxanes from novel sources are disclosed. Angiosperms other than hazelnut and the gymnosperm ginkgo have been discovered to be sources of taxane, including paclitaxel. Taxane may also be obtained from fungal endophytes from these plants. Methods for optimizing the recovery of taxane from plant sources are disclosed in which a plant part is surface-sterilized before extracting taxane therefrom or before culturing fungal endophytes therefrom.

Abstract: Isolated nucleic acid and amino acid sequences for phenylalanine aminomutase enzyme and methods for purifying this enzyme are provided. Methods for altering biosynthesis of compounds in plant cell cultures are also provided. In particular, methods for altering production of taxanes and taxane-related compounds are provided.

Abstract: The invention provides a process for the production of a biologically active phenolic compound (+) catechin from Taxus wallichiana tissue cultures, said process comprising the steps of (a) inoculating the of explants on a culture medium supplemented with combinations of auxins and cytokinins, (b) incubating the cultures under continuous light or dark conditions for 4-6 weeks for callus initiation followed by subculturing at 4-6 weeks intervals, (c) extracting the fresh pulverized calli with polar solvents at room temperature; (d) evaporating the solvent to obtain a residue; and (e) treating the residue with a chlorinated solvent and isolating (+) catechin compound by filtration.

Abstract: Oxygenase enzymes and the use of such enzymes to produce paclitaxel (Taxol®) related taxoids, as well as intermediates in the Taxol® biosynthetic pathway are disclosed. Also disclosed are nucleic acid sequences encoding the oxygenase enzymes. Particular oxygenase enzymes include the disclosed taxoid-14-beta hydroxylases.

Abstract: The invention concerns proteins of fungal origin having an epoxide hydrolase activity, such as those obtained in essentially pure form by extraction from fungi cells, or by culturing in host cells transformed by a nucleotide sequence coding for said fungal proteins. The invention also concerns the uses thereof, in particular for implementing methods for preparing enantiopure epoxides and/or diols.

Abstract: Compounds of the formula I 1

Abstract: The present invention relates to a compound named Percyquinnin that is obtainable by cultivating a basidiomycetes Stereum complicatum (DSM 13303), and to its pharmaceutically acceptable salts. The present invention further relates to a process for the production of Percyquinnin and to the use of Percyquinnin and its pharmaceutically acceptable salts as pharmaceuticals, in particular to their use as inhibitors of lipase.

Abstract: The present invention relate to a method to increase the production level of paclitaxel by changing the temperature during the plant cell culture. According to the present invention, the production of the paclitaxel comprises the following procedure: (i) cultivating the Taxus genus plant cells in a medium at ca. 20 to 25° C.; and (ii) when growth of the plant cells has progressed sufficiently, changing the cultivation temperature to ca. 26 to 32° C. to continue the culture. The present invention comprises also the method of increasing the paclitaxel production by inoculating the cells at a high initial concentration and by increasing the saccharide concentration in the medium: According to the present invention, paclitaxel can be mass-produced conveniently and therefore has an industrial application.

Abstract: Fermentation based methods for producing mycolactones allows one to produce large quantities of mycolactones, which can be purified by extraction and chromatography to yield pure preparations of mycolactones A, B, C, and D.

Abstract: The invention relates to a novel process that makes it possible to epoxidize &agr;,&bgr;-unsaturated enones or &agr;,&bgr;-unsaturated sulfones with high conversions and enantiomeric excesses in the presence of a water-soluble base, an oxidant, a diastereomer- and enantiomer-enriched homo-polyamino acid as catalyst, water, an organic solvent that is immiscible or has only limited miscibility with water, and a specific phase-transfer catalyst as cocatalyst.

Abstract: Recombinant Myxococcus host cells can be used to produce polyketides, including epothilone and epothilone analogs that can be purified from the fermentation broth and crystallized.

Abstract: The invention relates to a novel process that makes it possible to epoxidize &agr;,&bgr;-unsaturated enones or &agr;,&bgr;-unsaturated sulfones with high conversions and enantiomeric excesses in the presence of a water-soluble base, an oxidant, water, an organic solvent that is immiscible or has only limited miscibility with water, a preactivated diastereomer- and enantiomer-enriched homo-polyamino acid as catalyst, and a specific phase-transfer catalyst as cocatalyst.

Abstract: Methods for the enzymatic resolution of mixtures of enantiomers, such as &bgr;-lactam compounds, which may be employed as intermediates in the preparation of taxanes bearing a C-13 sidechain containing a heterocyclic or cycloalkyl group, the latter useful in the pharmaceutical field.

Abstract: The present invention related to microorganisms producing taxanes, such as paclitaxel or related taxanes, to the use of said microorganisms for the production of taxanes, and to the procedure for the isolation of said microorganisms from plants. In particular, the present invention relates to microorganisms of the Actinomycetes group producing taxanes as well as to the biologically pure cultures of a strain of the Actinomycetes group which produces taxanes. The microorganisms of Actinomycetes group are preferably belonging to the suprageneric groups of Streptomycetes, Actinoplanetes, Maduromycetes, Thermomonosporas or Nocardioforms, more preferably they are belonging to genus Streptomyces, Actinoplanes, Nocardiopsis, Micromonospora, Actinomadura or Kitasatosporia, still more preferably to the genus Kitasatosporia. A particularly preferred microorganism is Kitasatosporia sp. CECT 4991.

Abstract: A process for preparing baccatin and/or baccatin derivatives is described in which 10-deacetylbaccatin or a 10-deacetylbaccatin derivative is reacted in the presence of an isolated enzyme and an acetyl donor, the enzyme used being an acetyl transferase having a molecular weight of from 70 to 72 kD, determined by SDS-PAGE, which acetyl transferase is obtainable from Taxus chinensis cell cultures.

Abstract: A procedure for the preparation of pseudomonic acid A comprising submerged cultivation of a Pseudomonas bacterium strain capable of biosynthesis of the substantially pure pseudomonic acid A in aerated conditions via fermentation; and isolation of the desired compound is disclosed. In particular, the procedure of the present invention comprises cultivation of the Pseudomonas sp. bacterium strain No. 19/26 deposited under accession No. NCAIM(P)B 001235 in the National Collection of the Agricultural and Industrial Microorganisms, Budapest, Hungary, or its pseudomonic acid A-producing mutant or variant, on a medium at a temperature of between about 20° C. and 30° C. containing organic nitrogen and carbon sources and, optionally, mineral salts.

Abstract: A method for producing mevinolin by a microorganism in a fermentation process having a seed culture stage and a main fermentation stage, including a) cultivating a microorganism biomass in the seed culture stage to produce an inoculum; b) transferring the inoculum into a fermentation medium in the main fermentation stage; and, c) maintaining steady stage conditions in the main fermentation stage, thereby producing a fermentation broth containing mevinolin. Preferably, the steady state conditions are maintained in the main fermentation stage by one or more of feeding of organic carbon sources; controlling glucose and/or total reducing sugar content; feeding of organic nitrogen sources; controlling pH; controlling foam level; controlling the mass of the fermentation broth by withdrawals and feedings; and, controlling the dissolved oxygen level.

Abstract: A method has been discovered for the epoxidation of a compound having at least one carbon-carbon double bond, the method involves reacting a compound having at least one carbon-carbon double bond, a solvent, an oxidant, and membrane bound peroxygenase. Also discovered is a method for preparing the membrane bound peroxygenase involving grinding seeds containing peroxygenase to produce ground seeds, homogenizing the ground seeds in a buffer to form a slurry, centrifuging the slurry to produce a first supernatant, centrifuging the first supernatant to produce a second supernatant, and filtering said second supernatant through a protein-binding membrane filter to produce membrane bound peroxygenase; optionally the second supernatant is filtered through a hydrophilic membrane filter prior to filtering the second supernatant through a protein-binding membrane filter.

Abstract: The present invention relates to a method of producing a taxane-type diterpene wherein a cell and/or a tissue of a plant which produces the taxane-type diterpene is cultured in the presence of at least one substance selected from the group consisting of coronatines, a bacterium which produces the coronatines, a culture solution or a culture extract of such bacterium, cyclic polysaccharides, fatty acids, and an imino or amino derivative of jasmonic acids, then the taxane-type diterpene is recovered from the resulting cultures.

Abstract: A method for the continuous synthesis of baccatin-III is performed by means of the enzymatic acetylations of 10-deacetyl baccatin-III (10-DAB) in an enzyme reactor. This objective is accomplished by a method, for which an aqueous reaction batch is used, which contains a partially purified or a very pure acetyl transferase from a Taxus species and synthesis components, especially 10-DAB, acetyl compounds or optionally an acetyl coenzyme A, which can be regenerated, a protective colloid and optionally a buffer substance in solution. The solution is separated by a semipermeable membrane from an organic solvent, which serves as extraction agent for baccatin-III, the reaction batch being regenerated at regular intervals in an aqueous buffer system and the solvent continuously being exchanged. By conducting the reaction, the product can be removed continuously from the reaction batch for the partial synthesis of taxol and taxoter. By the above method, achievable yields are increased significantly.

Abstract: This invention relates to the isochroman compound of formula (I) and its pharmaceutically acceptable salts, which are useful as an amyloid aggregation inhibitor and for treating Alzheimer's disease. This invention also relates to processes for producing the isochroman compound, which comprises cultivating Penicillium simplicissimum FERM BP-6357 and then isolating the isochroman compound from the fermentation broth. The present invention also relates to a pharmaceutical composition comprising the isochroman compound.

Abstract: The present invention discloses a method for producing a taxane-type diterpene(s) by culturing cells of a taxane-type diterpene-producing plant, comprising one or both of the the following steps (a) and (b) to increase the ratio of those cell clusters suitable in size for diterpene production: (a) at least one operation for removing large cell clusters is conducted with a sieve and/or a filter during preculture of the cells to be supplied to main culture for the production of taxane-type diterpenes or at the time of cell transfer from one preculture to the subsequent preculture; (b) the cells are cultured under strong agitation conditions.

Abstract: Fermentation based methods for producing mycolactones allows one to produce large quantities of mycolactones, which can be purified by extraction and chromatography to yield pure preparations of mycolactones A, B, C, and D.

Abstract: This invention relates to a method of producing a taxane-type diterpene(s) wherein tissues or cells of a plant which produces taxane-type diterpene(s) is cultured in the presence of at least one selected from the group consisting of jasmonic acids, compounds containing a heavy metal, complex ions containing a heavy metal, heavy metal ions, amines and antiethylene agents, a method of producing a taxane-type diterpene wherein the tissues or the cells of the plant are cultured by controlling the oxygen concentration in a gas phase in a culture vessel to less than the oxygen concentration in the atmosphere from the initial stage of the culture, or by controlling the dissolved oxygen concentration in a fluid medium which is in contact with the tissue or the cell to less than the saturated dissolved oxygen concentration at that temperature from the initial stage of the culture, a method of producing a taxane-type diterpene wherein the tissue or the cell of the plant is cultured in a culture vessel, while oxygenic g

Abstract: The present invention relates to a process for the preparation of optically active 6-hydroxymethyl-4-tert-butyldimethylsilyloxy)-(4S,6R)-tetrahydro-2H-2-pyranone (&bgr; Hydroxy &dgr; Lacone) and the compound 3-oxo-5-(tert.

Abstract: A method of producing an &agr;-halo-&agr;,&bgr;-saturated carbonyl compound from an &agr;-halocarbonyl compound having an &agr;, &bgr;-carbon-carbon double bond by reducing said &agr;,&bgr;-carbon-carbon double bond using a microorganism belonging to any one of the genera Acetobacter, Actinomyces, Acinetobacter, Agrobacterium, Aeromonas, Alcaligenes, Arthrobacter, Azotobacter, Bacillus, Brevibacterium, Burkholderia, Cellulomonas, Corynebacterium, Enterobacter, Enterococcus, Escherichia, Flavobacterium, Gluconobacter, Halobacteium, Halococccus, Klebsiella, Lactobacillus, Microbacterium, Micrococcus, Micropolyspora, Mycobacterium, Nocardia, Pseudomonas, Pseudonocardia, Rhodococcus, Rhodobacter, Serratia, Staphylococcus, Streptococcus and Streptomyces, Xanthomonas, or a microbial product thereof. Pseudomonas sp. SD810, SD811 and SD812, Burkholderia sp.

Abstract: A flavoring solution for making pickles having a flavor of foods pickled in rice bran paste, a clear bran pickles flavoring solution, processes for producing the flavoring solutions, a process for producing lactones which are essential components of the flavoring solutions, and a bacterium belonging to the genus Corynebacterium which is useful for producing a lactone are disclosed. The bacterium is preferably Corynebacterium sp. NK-1 (FERM BP-6329). The lactone is preferably a &ggr; lactone.

Abstract: The present invention relates to a compound named Percyquinnin which is obtainable by cultivation of the fungus Basidiomycetes Stereum complicatum (DSM 13303), and to its pharmaceutically acceptable salts. The present invention further relates to a process for the production of Percyquinnin, to the microorganism Basidiomycetes Stereum complicatum (DSM 13303), to the use of Percyquinnin and its pharmaceutically acceptable salts as pharmaceuticals, in particular to their use as inhibitor of lipase, and to pharmaceutical compositions comprising Percyquinnin or a pharmaceutically acceptable salt thereof.

Abstract: A method of producing an &agr;-halo-&agr;,&bgr;-saturated carbonyl compound from an &agr;-halocarbonyl compound having an &agr;,&bgr;-carbon-carbon double bond by reducing said &agr;,&bgr;-carbon-carbon double bond using a microorganism belonging to any one of the genera Acetobacter, Actinomyces, Acinetobacter, Agrobacterium, Aeromonas, Alcaligenes, Arthrobacter, Azotobacter, Bacillus, Brevibacterium, Burkholderia, Cellulomonas, Corynebacterium, Enterobacter, Enterococcus, Escherichia, Flavobacterium, Gluconobacter, Halobacteium, Halococccus, Klebsiella, Lactobacillus, Microbacterium, Micrococcus, Micropolyspora, Mycobacterium, Nocardia, Pseudomonas, Pseudonocardia, Rhodococcus, Rhodobacter, Serratia, Staphylococcus, Streptococcus and Streptomyces, Xanthomonas, or a microbial product thereof. Pseudomonas sp. SD810, SD811 and SD812, Burkholderia sp.

Abstract: A process useful for the preparation of intermediates in synthesis or semi-synthesis of paclitaxel analogs wherein a starting taxane such as 10-deacetylbaccatin III is deacetylated at the C-4 position using a microorganism or an enzyme derived therefrom to provide 4-deacetyltaxanes, such as 4,10-dideacetylbaccatin III.

Abstract: This invention relates to a method of producing a taxane-type diterpene(s) wherein tissues or cells of a plant which produces taxane-type diterpene(s) is cultured in the presence of at least one selected from the group consisting of jasmonic acids, compounds containing a heavy metal, complex ions containing a heavy metal, heavy metal ions, amines and antiethylene agents, a method of producing a taxane-type diterpene wherein the tissues or the cells of the plant are cultured by controlling the oxygen concentration in a gas phase in a culture vessel to less than the oxygen concentration in the atmosphere from the initial stage of the culture, or by controlling the dissolved oxygen concentration in a fluid medium which is in contact with the tissue or the cell to less than the saturated dissolved oxygen concentration at that temperature from the initial stage of the culture, a method of producing a taxane-type diterpene wherein the tissue or the cell of the plant is cultured in a culture vessel, while oxygenic g

Abstract: The present invention has its object to provide a noble antifungal substance which is use of as clinical medicine in the therapy of fungal infectious diseases. The present invention is related to an antibiotic TKR459 having the following chemical formula (1) or its pharmacologically acceptable salt.

Abstract: The present invention has its object to provide a noble antifungal substance which is use of as clinical medicine in the therapy of fungal infectious diseases.

Abstract: The invention is a process for producing N-substituted glucamines, a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof, and a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof and reducing the oxidized N-substituted glucamine to an N-substituted-1-deoxynojirimycin. In addition, a one pot process for producing N-substituted-1-deoxynojirimycin from D-glucose is disclosed.

Abstract: Antibitic TKR2648 having the following chemical formula (I) or its pharmacologically acceptable salt.

Abstract: A method for derivatizing a compound having a hydroxyl group by back to back acylation is provided. The compound is acylated with a bifunctional acyl donor in the presence of a hydrolase to form an activated acyl ester or carbonate. Preferably the bifunctional acylating donor is a di(vinyl) ester or carbonate. The activated acyl ester or carbonate is then used to acylate a nucleophile in the presence of a lipase. The method of the invention provides regioselective enzymatic acylation of the base compound.

Abstract: The present invention provides a method for mass production of taxol which comprises adding sugar into a culture medium containing sugar in the course of semicontinuous culture of Taxus genus plant cell, and a universal method for mass production of taxol which comprises culturing Taxus genus plant cell in a culture medium containing sugar and AgNO3 as well. In accordance with the present invention, large amount of taxol can be produced with a high yield, simply by manipulating the culture condition of Taxus genus plant cell culture.

Abstract: A microbiological process for producing vanillin and other useful products from ferulic acid is disclosed. Vanillin and guaiacol are recovered from the process using a differential pH extraction where the guaiacol is recovered at a pH of greater than 9 and the vanillin is recovered at a pH of from about 5 to about 8.

Abstract: Xanthene compounds represented by the formula: wherein R1 is a carboxyl group which may be esterified or amidated; R2 is a hydrogen atom, a hydroxyl group, or a hydrocarbon group which may be substituted; R3 and R4 are the same or different and are a hydroxyl group which may be substituted; R5 and R6 are a hydrogen atom or a halogen atom; R7 is a hydrogen atom, a nitro group, a halogen atom, a hydrocarbon group which may be substituted, a heterocyclic group which may be substituted, or an acyl group which may be substituted; n is an integer of 0 to 2; and Y is an oxygen atom or two hydrogen atoms; and when n is 0, R2 may be a group represented by the formula: wherein the symbols have the same meanings as defined above, or a salt thereof inhibit a binding of B7-1 to CD28, prevent the B7-1-dependent activation of T cells and inhibit IL-2 production from T cells, thus being used as an immunomodulator such as a graft rejection inhibitor or a pharmaceutical composition for thera

Abstract: Disclosed are crystalline complexes of baccatin III with imidazole, 2-methylimidazole or isopropanol, which are useful for isolating baccatin III from plant tissue cell culture and plant extracts containing baccatin Ill.

Abstract: A method for producing lovastatin by a microorganism in a fermentation process having a seed culture stage and a main fermentation stage, including a) cultivating a microorganism biomass in the seed culture stage to produce an inoculum; b) transferring the inoculum into a fermentation medium in the main fermentation stage; and, c) maintaining steady stage conditions in the main fermentation stage, thereby producing a fermentation broth containing lovastatin. Preferably, the steady state conditions are maintained in the main fermentation stage by one or more of feeding of organic carbon sources; controlling glucose and/or total reducing sugar content; feeding of organic and/or inorganic nitrogen sources; controlling pH; controlling foam level; controlling the mass of the fermentation broth by withdrawals and feedings; and, controlling the dissolved oxygen level.

Abstract: An enzymatic hydroxylation method for the preparation of compounds useful as intermediates in the preparation of taxanes such as 6-.alpha.-hydroxy-7-deoxypaclitaxel, wherein one or more C-6 hydrogen-bearing taxanes are contacted with an enzyme or microorganism capable of hydroxylating said C-6 carbon to give C-6 hydroxyl-bearing taxane.

Abstract: A process for stereoselectively forming N-substituted dihydro-2,3 benzodiazepines which are useful as AMPA receptor antagonists. The process includes an opening reduction step which sets the stereochemistry of the intermediates and the final compounds to the desired enantiomer. The reduction step may be carried out by an enzymatic reduction.

Abstract: The present invention relates to a method of obtaining different biologically pure cultures of bacteria isolated from different species of Taxus such as Taxus canadensis. T. brevifolia, T. baccata, T. cuspidata, and T. hunnewelliana, wherein the bacteria produce in vitro taxanes and paclitaxel, and wherein the bacteria are of the genus Sphingomonas, Bacillus, Pantoea or Curtobacterium. Also, the present invention relates to a method of a bacterial mass production of at least one taxane or paclitaxel. There is also disclosed a novel bacterial taxane. The present invention also relates to the use of different biologically pure cultures of bacteria isolated from different species of Taxus, wherein the bacteria are able to biotransform pro-taxanes. There is also provided a process for improving taxanes and paclitaxel production of taxanes and paclitaxel producing bacteria which include culturing bacteria in the presence of a mutagenic agent for a period a time sufficient to allow mutagenesis.

Abstract: (2R,3S)- and (2S,3R)-enantiomers of trans-.beta.-phenylglycidic esters, prepared by lipase-mediated enantioselective transesterification, are used for the synthesis of the taxol C-13 side chain with good yield.

Abstract: Taxol is produced from taxol-producing micro-organisms. Methods of obtain the taxol-producing microorganisms are described. Radioactive labelled taxol products and methods for use of the radioactive labelled taxol and for the treatment of leukemia and cancer cells are described.

Abstract: A novel polypeptide, acylglucosamine 2-epimerase as shown in FIG. 1 and derivatives thereof, DNA coding for said enzyme, a recombinant vector containing said enzyme, a transformant integrated thereinto said vector, a method for producing said enzyme and a method for producing N-acetylmannosamine and N-acetylneuraminic acid using renin binding protein.

Abstract: This invention relates to a method of producing a taxane-type diterpene(s) wherein tissues or cells of a plant which produces taxane-type diterpene(s) is cultured in the presence of at least one selected from the group consisting of jasmonic acids, compounds containing a heavy metal, complex ions containing a heavy metal, heavy metal ions, amines and antiethylene agents, a method of producing a taxane-type diterpene wherein the tissues or the cells of the plant are cultured by controlling the oxygen concentration in a gas phase in a culture vessel to less than the oxygen concentration in the atmosphere from the initial stage of the culture, or by controlling the dissolved oxygen concentration in a fluid medium which is in contact with the tissue or the cell to less than the saturated dissolved oxygen concentration at that temperature from the initial stage of the culture, a method of producing a taxane-type diterpene wherein the tissue or the cell of the plant is cultured in a culture vessel, while oxygenic g

Abstract: Taxol is produced from taxol-producing microorganisms. Methods of obtaining he taxol-producing microorganisms are described. Radioactive labelled taxol products and methods for use of the radioactive labelled taxol and for the treatment of leukemia and cancer cells are described.