Abstract: A process for preparing optically active alkanols of the formula I in which n is an integer from 0 to 5; Cyc is an optionally substituted, mono- or polynuclear, saturated or unsaturated, carbocyclic or heterocyclic ring, and R1 is halogen, SH, OH, NO2, NR2R3 or NR2R3R4+X?, with R2, R3 and R4 independently of one another being hydrogen or a lower alkyl or lower alkoxy radical and X? being a counterion, which process comprises incubating in a medium comprising alkanone of the formula II in which n, Cyc and R1 are as defined above, an enzyme having a polypeptide sequence (i) SEQ ID NO: 1 or (ii) in which, compared to SEQ ID NO:1, up to 25% of the amino acid radicals have been altered by deletion, insertion, substitution or a combination thereof and which retains at least 50% of the enzymic activity of SEQ ID NO:1, with the compound of the formula II being enzymically reduced to give the compound of the formula I, and isolating the product formed.

Abstract: During the production of a product compound by fermentation, the concentration of a precursor compound is maintained within a pre-selected concentration range by having an adsorbent resin in contact with the culture medium. The adsorbent resin reversibly adsorbs precursor compound and, as un-adsorbed precursor compound is converted to product compound, adsorbed precursor compound is released from the resin, thus maintaining the concentration of precursor compound within the pre-selected range.

Abstract: The present invention discloses a new strain of Streptomyces sp. BICC 7522, its variants or mutants and use of the strain for the production of macrolides, process of production and purification of microlides.

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: An objective of the present invention is to provide a method for producing substance PF1022 derivatives, in particular PF1022-220 and PF1022-260, by a direct fermentation method, and a transformant to be used for this method. According to the present invention, there is provided a transformant producing substance FF1022 derivatives, which can be obtained by introducing a genes involved in a biosynthetic pathway from chorismic acid to p-aminophenylpyruvic acid, including a papA gene encoding 4-amino-4-deoxychorismate synthase. which gene comprises the DNA sequence encoding the amino acid sequence of SEQ ID NO: 2; a papB gene encoding 4-amino-4-deoxyclaismate mutase, which gene comprises the DNA sequence encoding the amino acid sequence of SEQ ID NO: 4; and a papC gene encoding 4-amino-4-deoxyprepbenate dehydrogenase, which gene comprises the DNA sequence encoding the amino acid sequence of SEQ ID NO: 6, into a phenylalanine auxotrophic host induced from an organism that produces a substance PF1022.

Abstract: The invention provides bradykinin antagonists and pharmaceutically acceptable salts thereof having anti-cancer activity. These anti-cancer compounds are particularly useful for inhibiting the growth of lung and prostate cancers.

Abstract: The present invention relates to proteins having an enzymatic activity of reducing substituted alkanones such as 3-methylamino-1-(2-thienyl)-propan-1-one. The invention furthermore relates to nucleic acids coding for said proteins, nucleic acid constructs, vectors, genetically modified microorganisms and to methods for preparing optically active substituted alkanols, such as, for example, (S)-3-methylamino-1-(2-thienyl)-(S)-propanol.

Abstract: The invention relates to a method for producing the optically active alkanols of formula (I), wherein n is an integer of from 0 to 5; Cyc represents an optionally substituted, mononuclear or polynuclear, saturated or unsaturated, carbocylic or heterocyclic ring, and R1 represents halogen, SH, OH, NO2, NR2R3 or NR2R3R4+X?, wherein R2, R3 and R4 independently represent H or a lower alkyl or lower alkoxy group and X? represents a counterion. According to the invention, an enzyme (E) selected from the groups of dehydrogenases, aldehyde reductases and carbonyl reductases is incubated in a medium containing the alkanone of formula (II), wherein n, Cyc and R1 are defined as above, in the presence of reduction equivalents.

Abstract: Three new alkaloids, Hirsutellones A, B, and C, are produced in cultures of fungus such as Hirsutella nivea strain BCC 2594 and Trichoderma sp. strain BCC 7579. The Hirsutellones exhibited potent growth inhibitory activity against Mycobacterium tuberculosis (H37Ra strain) with an MIC value of 0.78 ?g/ml, while showing weak or no cytotoxicity to mammalian cells. Therefore, Hirsutellones and pharmaceutical compositions containing Hirsutellones may be useful for the treatment of tuberculosis. Also described herein are methods of isolating the Hirsutellones.

Abstract: The present invention relates to fungal host cells that are transformed with a nucleic acid construct encoding a fungal oxygen-binding proteins or fragments thereof that comprise the oxygen-binding domain. Upon transformation of the host cell with the construct, the oxygen-binding protein confers to the host cell improved fermentation characteristics as compared to untransformed host cells. These characteristics include e.g. increases in oxygen uptake rates, biomass densities, volumetric productivities and/or product yields. The invention further relates to fermentation processes in which the host cells are used and to fungal oxygen binding proteins, in particular fungal flavohemoglobins and hemoglobin domains, and to nucleotides sequences encoding these proteins.

Abstract: The present invention relates to a novel source of microorganism for production of Camptothecin and related camptothecinoids. The invention also discloses its isolation, screening for Camptothecin production, growth, fermentation requirements and chemical analysis of Camptothecin (camptothecinoids).

Abstract: Migrastatin and a migrastatin analog can be produced by fermentation of Streptomyces platensis NRRL 18993 and used in pharmaceutical formulations to treat cancer and/or inhibit metastasis of cancer cells.

Abstract: The present inventors intended to search for substances that can regulate the expression of a molecular chaperone, GRP78, using the expression of GRP78 as an indicator. As a result, a novel tetronic acid derivative, versipelostatin compound (also known as JL68) shown in formula (I) having the activity of suppressing GRP78 expression was isolated from the metabolite of Streptomyces versipellis strain 4083-SVS6.

Abstract: A method for manufacturing (R)-tetrahydrothiophene-3-ol denoted by formula (II): by bioconversion of tetrahydrothiophene-3-one denoted by formula (I): to (R)-tetrahydrothiophene-3-ol denoted by formula (II). It comprises the steps of: (A) incubating the tetrahydrothiophene-3-one denoted by formula (I) in the presence of a strain, or a preparation of a cultured cell thereof, belonging to Penicillium, Aspergillus, or Streptomyces that is capable of said bioconversion; and (B) collecting the (R)-tetrahydrothiophene-3-ol denoted by formula (II) from incubated solution. A method for crystallization of optically active tetrahydrothiophene-3-ol of improved optical purity, characterized by maintaining a solution comprising optically active tetrahydrothiophene-3-ol and organic solvent at equal to or lower than 1° C.

Abstract: Granules that include a protein core are described. The protein core includes a protein matrix which includes a protein mixed together with a starch. The protein matrix can be layered over a seed particle or the protein core can be homogeneous. The protein can be an enzyme or a therapeutic protein.

Abstract: Microorganisms showing higher productivity of unusual-polyhydroxyalkanoate (PHA) than ever by using an inexpensive substrate or under specific conditions are obtained from wild strains and mutant strains. The microorganisms are cultured with such substrates to synthesize an unusual-polyhydroxyalkanoate. The unusual-polyhydroxyalkanoate can be produced with high efficiency at low cost.

Abstract: The present invention provides novel phenalenone derivatives of formula (I) which are formed by the microorganism Penicillium herquei Bainer & Sartory, DSM 14142, during fermentation.

Abstract: A microbial method for the preparation of an epothilone containing a terminal hydroxyalkyl group, comprising contacting at least one epothilone having a terminal alkyl group with an enzyme or microorganism capable of catalyzing the selective hydroxylation of said alkyl group to a hydroxyalkyl group, and effecting said hydroxylation.

Abstract: The invention relates to methods for reacting (di)amines as substrates in the presence of a lysine oxidase arid a reducing agent, resulting in alcohols, diols or cyclic secondary amines. In a particular embodiment, the invention is directed to methods of preparing cyclic secondary amines suitable for ultimately synthesizing piperidine-2-carboxylic acid and proline derivatives, useful, for example as thrombin inhibitors.

Abstract: A method for converting alkenes into epoxides and, particularly, to convert alkenes into enantio-specific epoxides by the use of enzymes which may be in their naturally-occuring (native) form or in mutated form, such as a native or mutated non-haem diiron-containing monooxygenase, and novel compounds produced thereby.

Abstract: The invention concerns methods for preparing pristinamycin IIA or IIB.

Abstract: Cost-effective processes for producing lactic acid and/or lactate from pentose-containing substrates, such as xylose-containing substrates, are provided. In particular, processes for producing lactic acid and/or lactate include fermentation of pentoses, such as xyloses, to enantiomerically pure lactic acid and/or lactate by moderately thermophilic Bacillus species. This fermentation runs by a homofermentive pathway and produces predominantly C3 compounds, so that C3 compounds can be recovered as lactic acid and/or lactate.

Abstract: The present invention provides compounds useful to inhibit tumor growth and to induce apoptosis. In general, the anti-cancer agents (ACA) are described by the formula: [ACA]n-X[Formula I] wherein X is a linker group having 2–5 functional groups or is absent, n=1, and ACA is selected from the group consisting of Formula II, Formula III, Formula IV, Formula V, and Formula VI, as described herein. Other compounds described herein are defined by the Formula VII, as described herein.

Abstract: A method for the resolution of a mixture of the cis or trans enantiomers of a compound of the formula wherein R1 is —O—C(O)alkyl, —O—C(O)aryl or —O—C(O)cycloalkyl by contacting the mixture with a carboxylic ester hydrolase enzyme which catalyzes the stereoselective hydrolysis of the mixture and the use of such enantiomers to produce antitumor compounds which are especially suitable for oral administration.

Abstract: A process for preparing enantiomer-enriched heterocyclic (R)- and (S)-cyanohydrins of the formula (I), where R1, R2, R3, R4 independently of one another are H, an unsubstituted or substituted C1–C24-alkyl, alkenyl or alkynyl radical, where one or more carbon atoms in the chain can be replaced by an oxygen atom, a nitrogen atom, a sulfur atom, an SO or an SO2 group, an unsubstituted or substituted aryl or heteroaryl radical or heterocyclic radical or halogen, hydroxyl, NR5R6, acetyl, oxo, C1–C6-carbalkoxy, C1–C6-carbalkoxyamino, COOR7, cyano, amide, benzoylamino or NO2, R5 and R6 are H, C1–C6-alkyl radical, phenyl radical, benzyl radical or COOR7, or together form a C2–C8-alkylene or heteroalkylene radical, R7 is H or C1–C6-alkyl, n is 0, 1, 2 or 3, X, Y and Z can be an unsubstituted or substituted carbon atom or a radical selected from the group consisting of N, O, S or NR5R6, where R5 and R6 are as defined above, SO or SO2, and at least one of the radicals X, Y and Z is not a carbon atom, where the compo

Abstract: A novel method of producing PS is described herein. The method first involves producing PLD enzyme through the use of enzyme-producing microorganisms. The PLD enzyme is reacted with a lecithin and source of serine to produce the phosphatidylserine (PS). The method differs from prior methods in several ways. First, it incorporates a novel strain of PLD enzyme-producing organism in a preferred embodiment. It is also the first known PS production method that allows for the reuse of the enzyme and serine components to enhance efficiency and productivity. It further incorporates a novel solvent system, unique stabilization agents for the PLD enzyme, as well as optimized reaction conditions.

Abstract: A process for the production of L-pipecolic acid which comprises the step of reducing delta-1-piperideine-6-carboxylic acid by the use of pyrroline-5-carboxylate reductase. The delta-1-piperideine-6-carboxylic acid is obtained by the step of converting L-lysine by the use of lysine 6-aminotransferase encoded by a gene of Flavobacterium lutescens. The steps of reducing delta-1-piperideine-6-carboxylic acid and the converting of L-lysine into L-pipecolic acid by the use of lysine 6-aminotransferase are carried out by using a bacterium transformed with a gene encoding lysine 6-aminotransferase wherein such bacterium comprises pyrroline-5-carboxylate reductase encoded by a gene of Escherichia coli or a coryneform bacterium. A recombinant bacterium which can be used in this production process is also provided. Thus, the present invention can provide an efficient biological process for the production of L-pipecolic acid (or 2-piperidinecarboxylic acid).

Abstract: The rapamycin gene cluster is an example of a gene cluster which includes a gene (rapL) leading to the formation of a precursor compound (pipecolic acid, in this case) which is required for inclusion in the larger product (rapamycin) produced by the enzymes encoded by the cluster. We have produced a mutant strain containing a rapamycin gene cluster in which the rapL gene is disabled. The strain does not naturally produce rapamycin but does so if fed with pipecolic acid. By feeding with alternative carboxylic acids we have produced variants of rapamycins. Tests have shown biological activity.

Abstract: Modifications of the peptide pyrrhocoricin permit the production of a variety of anti-bacterial or anti-fungal peptides having general formula R1-Asp-Lys-Gly-X-Y-Leu-Pro-Arg-Pro-Thr-Pro-Pro-Arg-Pro-Ile-Tyr-X?-Y?-R2 SEQ ID NO: 1 or multimeric compositions containing more than a single peptide of that formula. These peptides may be straight chain or cyclic peptides, and may contain one or more non-cleavable bonds. These peptides are characterized by anti-bacterial or anti-fungal activity and metabolic stability in mammalian serum. These peptides are useful in anti-bacterial or anti-fungal pharmaceutical compositions and for further drug development or identification of other antibiotic or anti-fungal compounds.

Abstract: The present invention relates to a novel antifungal antibacterial compound 2-methylheptylisonicotinate of formula 1 below obtained from natural sources and to a process for the isolation thereof.

Abstract: A method for the production of clavulanic acid by the fermentation of a clavulanic acid producing microorganism at a controlled level of at least 50 mg/l ammonia has been provided for. Under the application of these reaction conditions surprisingly high production levels of clavulanic acid have been obtained.

Abstract: A purified vitamin B6-phosphate phosphatase (VB6PP), having the following physico-chemical properties: a) Molecular weight: 29,000±5,000 (consisting of a monomer having a molecular weight of 29,000±5,000); b) Co-factor: Mn2+, Mg2+, Co2+, Sn2+, or Ni2+; c) Substrate specificity: active on pyridoxol 5?-phosphate, pyridoxal 5?-phosphate and pyridoxamine 5?-phosphate; d) Optimum temperature: 30–400° C. at pH 7.5; and e) Optimum pH: 7.0–8.0 is disclosed. Also disclosed are a process for producing VB6PP from a microorganism belonging to the genus Sinorhizobium capable of producing VB6PP, a process for producing vitamin B6 from vitamin B6-phosphate (VB6P) utilizing VB6PP, and a cell-free extract of a microorganism belonging to the genus Sinorhizobium capable of producing VB6PP.

Abstract: A process of flocculating microbial cell material from a suspending medium which contains cell material, comprising adding to the suspending medium a first polymeric material which is cationic and has intrinsic viscosity of not more than 2 dl/g, and subsequently or simultaneously adding to the suspending medium a second polymeric material which is cationic or substantially non-ionic and has intrinsic viscosity of at least 4 dl/g, and allowing the cell material to flocculate.

Abstract: A process for the resolution of enantiomeric mixtures of a chiral carboxylic acid, including an esterification reaction of the carboxylic acid in an organic solvent, in the presence of a stereoselective hydrolase, characterized in that an orthoester of the formula R1—C(OR2)3, in which R1 is selected from H and C1–C4alkyl and R2 is C1–C8alkyl or —CH2—C6-10aryl, is used as the esterification reactive.

Abstract: The present invention relates to a process for the preparation of the enantiomeric forms of 2-substituted 2-(2,5-dioxoimidazolidin-1-yl)acetic acid derivatives of the formula I, wherein R1, R2 and R3 have the meanings given in the claims, by stereodifferentiating conversion of mixtures of the enantiomers with the aid of enzymes.

Abstract: A microorganism strain which is Streptomyces griseus FERM BP-5420 and processes for preparing compounds by cultivating such microorganism strain.

Abstract: The inventon relates to an enzymatic method for the enantioselective reduction of organic keto compounds to the corresponding chiral hydroxy compounds, an alcohol dehydrogenase from Lactobacillus minor and a method for the enantioselective production of (S)-hydroxy compounds from a racemate.

Abstract: The present invention relates to a novel FKA-25 substance, which inhibits formation of the foam macrophage originated from mouse, having inhibitory action against formation of the foam macrophage and a process for production thereof. The process includes culturing Pseudobotrytis sp. FKA-25 belonging to genus Pseudobotrytis sp. and having ability to produce FKA-25 substance in a medium, accumulating FKA-25 substance in the cultured medium, and collecting FKA-25 substance from the cultured mass. The obtained FKA-25 substance specifically inhibits the formation of the foam macrophage originated from mouse and is expected to be useful for prevention and treatment of arteriosclerosis and causative diseases therefrom.

Abstract: Provided is a method of deprotecting a hydroxide or amine protected with a group of formula ArC*(R)H—(CH2)n—O—C(═O)— where the substituents are as described below, the method comprising: contacting the protected hydroxide or amine with an enzyme effective to remove the protecting group; and recovering the amine. Also provided is a method of isolating a bacteria producing an enzyme effective to remove a protecting group comprising: growing prospective bacteria on a medium having a growth selective amount of an amine compound that is protected as above; and isolating bacteria that grow on said medium.

Abstract: Engineered microorganisms that produce at least 200 &mgr;g alpha-lipoic acid (ALA) per g dry cell weight and engineered microorganisms that secrete at least a 2-fold greater amount of ALA than an amount of ALA found intracellularly, are described.

Abstract: In a process for preparing mevinolin by fermentation of a biomass in a fermentation liquor, which includes dissolving mevinolin from the biomass into the fermentation liquor, and separating the biomass from the fermentation liquor to obtain a separated fermentation liquor, separating the mevinolin from the separated fermentation liquor, and recovering the end product, the improvement which comprises carrying out the dissolving at a pH between 7.5 and about 10, and the separating of the mevinolin is carried out at a pH between about 4.5 and about 1.

Abstract: There is disclosed an improved poppy straw of a stably reproducing Papaver somniferum for the extraction of thebaine and/or oripavine, the threshed straw having thebaine and oripavine constituting about 50% by weight or greater of the alkaloid combination consisting of morphine, codeine, thebaine and oripavine.

Abstract: A chemoenzymatic process for the stereoselective preparation of both the (R) and (S) enantiomers of 3-hydroxy-3-(2-thienyl) propanenitrile has been developed. These optically pure key intermediates were prepared by enzymatic resolution of (+)3-hydroxy-3-(2-thienyl) propanenitrile both by transesterification and by hydrolysis reaction which were then transformed to both enantiomers of duloxetine.

Abstract: A microbial method for the preparation of an epothilone containing a terminal hydroxyalkyl group, comprising contacting at least one epothilone having a terminal alkyl group with an enzyme or microorganism capable of catalyzing the selective hydroxylation of said alkyl group to a hydroxyalkyl group, and effecting said hydroxylation.

Abstract: A polyhydroxyalkanoate characterized by having in the molecule a unit represented by Chemical Formula (1): wherein n may assume any one integral value within the range of from 1 to 8. Also disclosed are a process for producing the polyhydroxyalkanoate by the use of a microorganism having the ability to produce the polyhydroxyalkanoate and accumulate it in the bacterial body; a charge control agent, a toner binder and a toner which contain this polyhydroxyalkanoate; and an image-forming method and an image-forming apparatus which make use of the toner.

Abstract: Migrastatin and a migrastatin analog can be produced by fermentation of Streptomyces platensis NRRL 18993 and used in pharmaceutical formulations to treat cancer and/or inhibit metastasis of cancer cells.

Abstract: The present invention relates to processes for the microbial oxidation of bicyclic heteroaromatic compounds which comprise contacting these compounds with a microorganism, or a suitable mutant thereof, and incubating the resulting mixture under conditions sufficient to yield an amount of their respective carboxylic acids. The present processes optionally further comprise the isolation and purification of the product carboxylic acids.

Abstract: There is disclosed an improved poppy straw of a stably reproducing Papaver somniferum for the extraction of thebaine and/or oripavine, the threshed straw having thebaine and oripavine constituting about 50% by weight or greater of the alkaloid combination consisting of morphine, codeine, thebaine and oripavine.

Abstract: The invention relates to a microbiological process for preparing chiral arylalkanols by enantioselectively hydroxylating arylalkanes in the presence of a microorganism's host cells which are expressing the genes for oxygenases.

Abstract: PHA containing a novel 3-hydroxy-thioalkanoic acid unit having a highly reactive thienyl group in a side chain thereof, and a method of producing the same are provided. Specifically, 5-(2-thienyl-sulfanyl)valeric acid represented by Chemical Formula [4] below and 6-(2-thienylsulfanyl)hexanoic acid represented by Chemical Formula [5] below are provided. Further, a method of producing PHA, comprising the step of collecting PHA from cells of a microorganism cultured in a medium containing the valeric acid or hexanoic acid, and a novel PHA represented by Chemical Formula [1] below are provided.