Abstract: To provide a semaphorin inhibitor; a peripheral or central nerve regeneration promoter which contains said semaphorin inhibitor as an active ingredient; and a preventive or remedy for a neuropathic disease and a neurodegenerative disease containing said nerve regeneration promoter, or the like.

Abstract: The present invention provides a fermentation process for producing lipstatin comprising the steps of: a) preparing a fermentation medium containing a lipstatin-producing microorganism comprising an oil and an assimilable carbon source, wherein the wt/wt ratio of oil and assimilable carbon source is regulated to achieve an optimal lipstatin biosynthesis by the microorganism; and b) feeding the fermentation medium with an emulsifier, wherein the emulsifier provides an optimal viscosity for the fermentation medium and optimal pH during the fermentation to permit fermentation for lipstatin production. The disclosed process also provides a process for extracting a lipstatin from a fermentation broth.

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.

Abstract: A method for isolation of proanthocyanidins from flavonoid-producing cell cultures is disclosed. More specifically, the invention relates to the isolation of catechin, epicatechin, proanthocyanidin B-2, and other proanthocyanidins from Vaccinium pahalae Skottsberg cultures. The invention also provides a method for modifying the content of proanthocyanidins in a flavonoid-producing culture. Further, the invention relates to a method of performing metabolic studies with proanthocyanidins.

Abstract: A method for converting compactin to pravastatin is described. Compactin is provided and contacted with an agent derived from Actinomadura under conditions in which the agent converts compactin to pravastatin. Also described are an Actinomadura strain, an Actinomadura cell free extract, an Actinomadura hydroxylase, and a method for lowering cholesterol levels in mammals.

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: The invention relates to a means for enhancing the value of distillation residues of fermentation products and in particular, a process for producing compounds of economic interest from these distillation residues of fermentation products. This production process also comprises suitable steps for extracting these compounds. In particular, the invention relates to enhancing the value of distillation residues of fermentation products from the agro-feeding industry.

Abstract: An improved fermentation process for preparing pseudomonic acid A (mupirocin) is disclosed. The metabolically controlled fermentation process provides culturing a Pseudomonas sp. strain in a submerged medium at a temperature within about 20-30° C. The pH of the fermentation medium is regulated to be at about 5.5-6.0 by feeding the fermentation medium with an assimilable carbon source, a mineral salt, or an acidic/alkali solution. Accordingly, the resulting fermentation broth contains an increased yield of highly purified pseudomonic acid A as the main component. The pseudomonic acid B as an impurity in the fermentation broth is significantly decreased.

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 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: The invention relates to a compound of formula (I) wherein R1 is a sugar; R2 is —CH2—O—(R7)m, R7 representing a sugar, or is —COOH; R3 is an epoxide-comprising group, or is C1-C6-alkyl or C2-C6-alkenyl, unsubstituted or substituted by at least one OH; R5 is H, C1-C6-alkyl, C2-C6-alkenyl or C2-C6-alkynyl; R4R6, R8 and R10 independently of one another are H; C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, —X2H, or —X2R12, or R4 and R6 together and/or R8 and R10 together are =X2; X2 is O, NH, N—C1-C6-alkyl, N—C2-C6-alkenyl, N-C2-C6-alkynyl or S; R12 is C1-C6-alkyl, C2-C6—alkenyl, C2-C6-alkynyl, aryl or acyl; and m and n are 1 or 2; in any of its stereochemical forms and mixtures of these forms in any ratio, and a physiologically acceptable salt or derivative thereof. The compounds are obtainable from a culture of the microorganism Actinomycetales species HAG 003959, DSM 12931, by fermentation.

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: Disclosed is a process for producing a compound represented by general formula (II-a): (wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or an alkali metal; and R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compound (II-a)] or the lactone form of Compound (II-a) [hereinafter referred to as Compound (II-b)] which comprises subjecting a compound represented by general formula (I-a): (wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or an alkali metal; and R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compound (I-a)] or the lactone form of Compound (I-a) [hereinafter referred to as Compound (I-b)] to the action of an enzyme source derived from a microorganism belonging to the genus Bacillus and capable of converting Compound (I-a) or Compound (I-b) into Compound (II-a) or Comp

Abstract: A calorimetric assay system to measure the expression or activity of membrane-type matrix metalloproteinases using a thiopeptolide substrate. The subject colorimetric assay system is useful in screening pharmacological agents that may have therapeutic potential in the treatment of glaucoma and the promotion of wound healing. The subject colorimetric assay system is also useful in the discovery of new therapies for cancer and conditions involving neovascularization based on modulation of extracellular matrix.

Abstract: A process is provided for producing &ggr;-decalactone using Yarrowia lipolytica HR 145 (DSM 12397). The process includes preparing the product in a bioreactor by culturing the pure strain of Yarrowia lipolytica in a culture medium containing carbon compounds, nitrogen compounds, inorganic salts, trace elements, vitamins, etc. Other ingredients of the culture medium include glycerol, glucose, mannitol, citric acid, malt extract, yeast extract, casein hydrolysate, castor oil, cotton seed meal or corn steep liquor. Also sulphates, nitrates, chlorides, carbonates or phosphates of metals sodium, potassium magnesium, manganese, calcium, zinc, and mixtures thereof can be used in the culture medium. Further, a pure strain of Yarrowia lipolytica HR 145 (DSM 12397) is provided.

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: A method of increasing the production of lovastatin or monacolin J in a lovastatin-producing or non-lovastatin-producing organism is disclosed. In one embodiment, the method comprises the steps of transforming an organism with the A. terreus D4B segment, wherein the segment is translated and where an increase in lovastatin production occurs.

Abstract: A process for purifying statin compounds from a fermentation broth by extraction and crystallization is disclosed. A fermentation broth is subjected to a pretreatment procedure which involves an alkaline pretreatment and an alkaline purification. Following the pretreatment procedure, the statin compound is extracted under acidic conditions into a hydrophobic solvent and purified by crystallization. The organic extraction solvent is concentrated and then extracted with a mild base. The statin compound is then purified by crystallization.

Abstract: Optically active 2-substituted tetrahydropyran-4-ols or esters thereof may be prepared using esterases or hydrolases from the corresponding racemic mixtures of esters or alcohols. This provides a route to the corresponding optically active ketones.

Abstract: The very effective conversion of ML-236B substances and derivatives thereof into 6′-hydroxylated products with the microorganisms of species Amycolatopsis orientalis, or with an extract or a hydroxylation-effective enzyme derived from said microorganism, is described. The products obtained are suitable as HMG-CoA reductase inhibitors or intermediates thereof. Thus, the products can be used, for example, as an antihypercholesterolemic in pharmacy.

Abstract: &agr;-Hydroxy-&ggr;-carboxymuconic acid-&egr;-semialdehyde dehydrogenase, a gene encoding the enzyme, a recombinant vector containing the gene and a transformant carrying the gene, and processes for producing the enzyme and 2-pyrone-dicarboxylic acid by using the transformant. Use of the transformant can produce &agr;-hydroxy-&ggr;-carboxymuconic acid-&egr;-semialdehyde dehydrogenase in a large amount, thereby permitting industrial production of 2-pyrone-4,6-dicarboxylic acid.

Abstract: Disclosed is a method for preparing an R- or S-forms of &agr;-substituted heterocyclic carboxylic acid (&agr;-HCCA) and a counter enantiomeric form of &agr;-substituted heterocyclic carboxylic acid ester thereto by use of an enzyme. A racemic &agr;-HCCA is reacted with alcohol to give a racemic &agr;-HCCA ester, which is then brought into contact with an enzyme with enantioselectivity, whereby either R-form or S-form of the racemate is hydrolyzed. Extraction with an organic solvent can obtain enantiomers of the &agr;-HCCA ester. Thus, a certain enantiomeric form of &agr;-HCCA and a counter enantiomeric form of &agr;-HCCA ester thereto, respectively can be prepared with high optical purity at high yields as well as at low cost.

Abstract: Disclosed is a process for producing a compound represented by general formula (II-a): 1

Abstract: Disclosed in this invention are a novel enzyme producing tartaric acid ether compound which catalyzes a reaction of producing a tartaric acid ether compound in which the phenolic hydroxyl group(s) of a flavonoid or its analogous compound having at least one phenolic hydroxyl group is (are) acted to the epoxy ring of an epoxysuccinic acid to form ether linkage of one or more tartaric acid residues, a process for producing a tartaric acid ether compound by acting the enzyme in the presence of an epoxy-succinic acid and a flavonoid or its analogous compound having at least one phenolic hydroxyl group, and novel tartaric acid ether compounds in which the epoxy ring of an epoxysuccinic acid is bound to the phenolic hydroxyl group(s) of a flavonoid or its analogous compound to form ether linkage of one or more tartaric acid residues. These compounds are useful as a component material of pharmaceuticals and functional foods.

Abstract: A novel microorganism, Penicillium citrinum CCRC 930024 and a process of using the microorganism for the production of compactin comprising cultivating Penicillium citrinum CCRC 930024 in a fermentation medium and recovering compactin from the fermentation broth are disclosed.

Abstract: The present invention is related to a new microorganism Streptomyces exfoliatus YJ-118 and a method for producing pravastatin sodium by using this microorganism which shows a strong tolerance to ML-236B and a high hydroxylation activity of ML-236B to pravastatin.

Abstract: Optically active chroman-3-acetic acids and optically active chroman-3-acetic acid esters can be obtained by treating a mixture of (3R)- and (3S)-chroman-3-acetic esters of formula (I) [wherein R1 is a straight or branched alkyl group having 1-5 carbon atoms and R2 is a hydrogen atom or substituted or unsubstituted amino group] is treated with an esterase which has an optically selective hydrolyzing activity or microorganisms which carry said hydrolase, or a preparation therefrom. A novel esterase derived from bacteria of genus Pseudonocardia can also be used as said esterase.

Abstract: A method of producing (S)-3-[2-{(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methane sulfonate using 1,3-butadiene and a ketoethanal to form an intermediate racemic mixture. The racemic mixture is resolved to remove one isomer from the reaction product mixture. Following resolution, the following steps are performed: reduce the isomer to an alcohol, react the alcohol with triphenylmethyl chloride, ozonalyze the resulting reaction product, reduce the ozonalyzed product to yield a diol and react the diol with a methane sulfonyl compound to form (S)-3-[2-{(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methane sulfonate. Alternatively, the racemic mixture may first be reduced and the resulting racemic alcohol mixture is resolved to isolate one isomer of the alcohol and the remaining process steps are followed.

Abstract: A method for converting compactin to pravastatin is described. Compactin is provided and contacted with an agent derived from Actinomadura under conditions in which the agent converts compactin to pravastatin. Also described are an Actinomadura strain, an Actinomadura cell free extract, an Actinomadura hydroxylase, and a method for lowering cholesterol levels in mammals.

Abstract: A method of reducing the percentage of Epstein-Barr virus genome-carrying cells which exhibit Epstein-Barr virus early antigen induction, where the Epstein-Barr virus genome-carrying cells have been cultivated in the presence of at least one tumor-promoting or tumor-inducing chemical. The method is carried out by cultivating Epstein-Barr virus genome-carrying cells in the presence of a tumor-promoting or tumor-inducing chemical; and treating the Epstein-Barr virus genome-carrying cells with a synthetic fluorescein dye. The dyes effectively reduce the incidence of Epstein-Barr virus early antigen induction in the cultivated Epstein-Barr virus genome-carrying cells.

Abstract: A method for converting compactin to pravastatin is described. Compactin is provided and contacted with an agent derived from Actinomadura under conditions in which the agent converts compactin to pravastatin. Also described are an Actinomadura strain, an Actinomadura cell free extract, an Actinomadura hydroxylase, and a method for lowering cholesterol levels in mammals.

Abstract: An isoflavone aglycone-containing composition having genistein as a main aglycone is produced by a process comprising allowing a protease and &bgr;-glucosidase to act on a soy protein raw material, an extract of a soy protein raw material or a by-product of a soy protein raw material to water-solubilize the protein of soybean origin and to convert isoflavone glycosides to the corresponding aglycones, separating water-soluble components from the enzymatic reaction mixture, and recovering water-insoluble matter.

Abstract: The invention provides a simple and selective method for the deacylation of 4-acylated statins during the preparation of statins from a fermentation broth, more specifically a reduction of impurities from the process, by increasing the pH of the fermentation broth.

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

Abstract: Natural product metabolites produced by fungi are synthesized using fungal spores that have been immobilized onto/into a support. Supports that can be used include loofah sponge, synthetic sponge, powdered cellulose paper, wood shavings, calcium alginate gel beads, agar gel beads, channeled aluminum beads, polypropylene beads and glass beads. Immobilizing the fungal spores provides accelerated production of the natural product metabolite in a standard bioreactor. Fungi that can be used include Penicillium cyclopium, Penicillium chrysogenum, Penicillium citrinum, Trichoderma viride, Aspergillus terreus and Monascus ruber. In a preferred embodiment, spores of Penicillium cyclopium NRRL 6233 immobilized with loofah sponge are cultured in a nutrient media for at least 4 days to produce compactin which is a hypocholesteremic agent.

Abstract: A process for macromolecularizing phenolic compounds or aromatic amine compounds by the action of a catalyst comprising an enzyme having a polyphenol oxidizing activity in the alkali region; applications of the compounds obtained by the above process to thickeners, stabilizers, coagulants, emulsifiers, dispersants, water retainers, antioxidants, adhesives, concrete admixtures, dyes, coating materials, petroleum recovering agent, soil conditioner, a blow-applied seed bearing surface soil stabilizer, deodorants, smell eliminators, agricultural chemical spreaders, feeding stuff binders, bactericides, antimicrobial agents, viral infection inhibitors, bioadhesion preventives, biotic repellents, insecticides, poultices, ink bases or wood treating agents; and method of waste water disposal, a method of deoxygenation and a method of treating wood, concrete or soil in which use is made of the above reaction.

Abstract: Optically active 2-substituted tetrahydropyran-4-ols or esters thereof may be prepared using esterases or hydrolases from the corresponding racemic mixtures of esters or alcohols. This provides a route to the corresponding optically active ketones. The racemic mixtures are preferably in the cis-form. such mixtures may be produced by-reacting but-3-ene-1-ol with an aldehyde in the presence of an acid.

Abstract: Disclosed is a process for producing a compound represented by general formula (II-a): (wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or an alkali metal; and R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compound (II-a)] or the lactone form of Compound (II-a) [hereinafter referred to as Compound (II-b)] which comprises subjecting a compound represented by general formula (I-a): (wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or an alkali metal; and R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compound (I-a)] or the lactone form of Compound (I-a) [hereinafter referred to as Compound (I-b)] to the action of an enzyme source derived from a microorganism belonging to the genus Bacillus and capable of converting Compound (I-a) or Compound (I-b) into Compound (II-a) or Comp

Abstract: The present invention relates to a process for preparing isoflavone aglucone using Rhodotorula glutinis, more specifically, to a novel Rhodotorula glutinis strain (KCCM-10172) which can be isolated from fermented soybeans and has a good ability to convert into isolfavone aglucone, and a process for preparing isoflavone aglucone using the said strain which comprises culture for 30-54 hours in a condition of pH 4.0-8.0 and 25-35° C. using an extract from soybeans or germs of soybeans as a medium and control of content of dissolved oxygen to produce isoflavone containing aglucone of a purity of 90% or more.

Abstract: The invention provides a method of producing &agr;-tocopherol and &agr;-tocopheryl esters. The method comprises using a biological system to produce farnesol or geranylgeraniol. Then, the farnesol or geranylgernaiol is chemically converted into &agr;-tocopherol or an &agr;-tocopheryl ester.

Abstract: The present invention is related to a new method for producing ML-236B, a precursor of pravastatin sodium, in particular to a method for producing ML-236B lactone form(I), free acid form(II), sodium salt(III) shown in the formulae (I), (II), (III) by using a new microorganism isolated from soil. ML-236B is obtained from the culture broth of this microorganism and it is used as a substrate of pravastatin sodium which is a potent cholesterol-lowering agent used in treatment for hypercholesterolemia.

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: A two phase environmentally friendly fermentation process for producing high yields of &dgr;-decalactone and &dgr;-dodecalactone from the corresponding unsaturated starting materials is carried out under oxidative growth conditions using a saccharomyces species. The resulting products impart, augment and/or enhance the aroma and/or taste of consumable materials including foodstuffs, chewing gums, toothpastes, beverages, fragrance compositions, colognes and perfumed articles such as solid or liquid, anionic, cationic, non-ionic or zwitterionic detergents, fabric softeners, and hair preparations.

Abstract: The invention relates to a process for the preparation of (−)-3,4-trans-compounds involving an enzymatic hydrolysis. These compounds and their salts are useful in the treatment of bone loss, hyperlipoproteinaemia, hypertriglyceridaemia, hyperlipidaemia, or hypercholes-terolaemia or arteriosclerosis or in anticoagulative treatment.

Abstract: DNA encoding triol polyketide synthase (TPKS) has been isolated, purified and sequenced. Expression vectors comprising TPKS, cells transformed with the expression vectors, and processes employing the transformed cells are provided.

Abstract: A fermentation process is disclosed for producing an HMG-CoA reductase inhibitor such as lovastatin or compactin. In particular, it relates to a process wherein at least part of the assimilable nitrogen source and, optionally, the carbon source is provided continuously or intermittently to the culture.

Abstract: Processes for the production of isoflavones are described wherein plant material from plants of the genus leguminosae are contacted with water, an enzyme which cleaves isoflavone glycosides to the aglucone form and a C.sub.2 -C.sub.10 organic solvent, so as to form a combination, incubating the combination for a time sufficient to allow isoflavones of the aglucone form to partition into the organic solvent component, and thereafter recovering isoflavones from the organic solvent component.

Abstract: A process for producing high yields of .gamma.-hexalactone and 2-pentanone from the corresponding hexanoic acid starting material is carried out with high amounts of oxygen and sugar in the presence of a mold microorganism. Fragrance compositions and foodstuff compositions are augmented and enhanced by the presence of the product compounds.

Abstract: Optically active chroman-3-acetic acids and optically active chroman-3-acetic acid esters can be obtained by treating a mixture of (3R)- and (3S)-chroman-3-acetic esters of formula (I) ##STR1## [wherein R.sub.1 is a straight or branched alkyl group having 1-5 carbon atoms and R.sub.2 is a hydrogen atom or substituted or unsubstituted amino group]is treated with an esterase which has an optically selective hydrolyzing activity or microorganisms which carry said hydrolase, or a preparation therefrom. A novel esterase derived from bacteria of genus Pseudonocardia can also be used as said esterase.

Abstract: An enzymatic hydroxylation process for the preparation of compounds useful as HMG-CoA reductase inhibitors and/or as intermediates in the preparation of HMG-CoA reductase inhibitors uses a microorganism or an enzyme derived from, or having the structure of an enzyme derived from, said microorganism, which is capable of catalyzing the hydroxylation process.