Abstract: There is provided a process for the preparation of a chiral insecticidal and acaricidal compound of formula I. Also provided are intermediate compounds useful in the process of the present invention.

Abstract: The invention relates to a new process for concentrating epothilones in culture media, a new process for the production of epothilones, a new process for separating epothilones A and B and a new strain obtained by mutagenesis for the production of epothilones, as well as aspects related thereto. New crystal forms of epothilone B are also described.

Abstract: In the biosynthetic reaction system of caffeine, enzymes which catalyze these reactions respectively, and a method of composite utilization of genes encoding these enzymes, respectively are provided. A process for producing 7-methylxanthine, theobromine or caffeine which comprises methylation of xanthosine, ribose removal of 7-methylxanthosine, methylation of 7-methylxanthine, and/or methylation of theobromine ex vivo, in the presence of a combination of two or more of the enzymes a, c and d, and the cellular extract b.

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: 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 provides new substantially pure antibiotics designated AC-98-1, AC-98-2, AC-98-3, AC-98-4 and AC-98-5 derived from the microorganism Streptomyces hygroscopicus.

Abstract: Methods for the manufacture of Mycophenolate are disclosed. Mycophenblate mofetil is biochemically synthesized using Mycophenolic Acid and 2-morpholino ethanol with the help of an enzyme. Mycophenolate mofetil is also chemically synthesized non-catalytically by refluxing mycophenolic acid with 2-morpholino ethanol in the absence of a third solvent or a catalyst.

Abstract: Known microbiological methods are based upon the application of pigment-forming bacteria, in particular chromobacterium violaceum. The yield of these methods is very low, however, so that large industrial applications are not possible. However, in many fields of industry, there exists a very great demand for natural blue dyes which are substantially suitable for human digestion, which cannot be satisfied at present. Therefore, the method in accordance with the invention is characterized by the application of the newly discovered marine sediment bacterium pseudoalteromonas spezies of the “Black Beauty” strain (originally deposited under file number DSM 13623 with the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH., Braunschweig, Germany pursuant to the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure). Compared to conventional methods, this marine sediment bacterium leads to an about thirteen-fold yield.

Abstract: The present invention relates to compounds made by a subset of modules from one or more polyketide synthase (“PKS”) genes that are used as starting material in the chemical synthesis of novel molecules, particularly naturally occurring polyketides or derivatives thereof. The biologically derived intermediates (“bio-intermediates”) generally represent particularly difficult compounds to synthesize using traditional chemical approaches due to one or more stereocenters. In one aspect of the invention, an intermediate in the synthesis of epothilone is provided that feeds into the synthetic protocol of Danishefsky and co-workers. In another aspect of the invention, intermediates in the synthesis of discodermolide are provided that feed into the synthetic protocol of Smith and co-workers.

Abstract: The present invention provides a generalized oxygen-limited cultivation method for myxobacterial strains engineered to heterologously express polyketides synthase (PKS) gene clusters under various oxygen tension conditions, modulating the polyketide congener distribution.

Abstract: The invention concerns methods for preparing pristinamycin IIB and methods for preparing modified pristinamycin IIB.

Abstract: The invention relates to a new process for concentrating epothilones in culture media, a new process for the production of epothilones, a new process for separating epothilones A and B and a new strain obtained by mutagenesis for the production of epothilones, as well as aspects related thereto. New crystal forms of epothilone B are also described.

Abstract: An isolated DNA fragment encoding a protein with CAD activity wherein the protein is clavulanic acid dehydrogenase (CAD) from S. clavuligerus, with the proviso that the isolated DNA fragment is not: (a) the 13.1 kb BglII to SphI fragment of S. clavuligerus; (b) the 10.8 kb EcoRI to BamHI fragment of S. clavuligerus; (c) the 8.8 kb BclI to BclII fragment of S. clavuligerus; (d) the 2.5 kb BglII to BglII fragment of S. clavuligerus; (e) the 60 kb BglII to BamHI fragment of S. clavuligerus; or (f) the 18.0 BclI to SphI fragment of S. clavuligerus.

Abstract: The invention relates to a new process for concentrating epothilones in culture media, a new process for the production of epothilones, a new process for separating epothilones A and B and a new strain obtained by mutagenesis for the production of epothilones, as well as aspects related thereto. New crystal forms of epothilone B are also described.

Abstract: DNA sequences are provided which encode the enzymes required for clavulanic acid synthesis. A process is provided for producing clavulanic acid in a transformant of a non-clavulanate-producing host.

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: The present invention provides processes useful in the preparation of certain &bgr;3-adrenergic receptor agonists of the structural formula 1

Abstract: The invention relates to a new process for concentrating epothilones in culture media, a new process for the production of epothilones, a new process for separating epothilones A and B and a new strain obtained by mutagenesis for the production of epothilones, as well as aspects related thereto. New crystal forms of epothilone B are also described.

Abstract: This invention relates to an isolated nucleic acid fragment encoding a biotin synthases. The invention also relates to the construction of a chimeric gene encoding all or a portion of the biotin synthases, in sense or antisense orientation, wherein expression of the chimeric gene results in production of altered levels of the biotin synthases in a transformed host cell.

Abstract: Isolated nucleic acid sequences and polypeptides encoded thereby for epothilone B hydroxylase and mutants and variants thereof and a ferredoxin located downstream from the epothilone B hydroxylase gene are provided. Also provided are vectors and cells containing these vectors. In addition, methods for producing recombinant microorganisms, methods for using these recombinant microorganism to produce hydroxyalkyl-bearing epothilones and an epothilone analog produced by a mutant of epothilone B hydroxylase 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: Cis-&bgr;-lactam compounds having structure (II) are described herein which are prepared by enantioselective acylation of the free amine in the presence of Penicillin G Amidase.

Abstract: The following invention relates to a process for oxidizing alkyl groups attached directly or via a linker, to a sulfonamide moiety (II) by the use of cytochrome P450 enzymes, to give the corresponding alcohol or carboxylic acid (I). wherein R is an organic radical, X is a linker, Y is —C(CH3)2— or —CH(CH3)— and Z is —CH2OH or —COOH.

Abstract: Fluorescent dye compounds of formula (I) are disclosed. These compounds are useful as they interact with organic compounds in a manner such that excitation with certain wavelengths of light results in fluorescent emmission. Detection and/or monitoring of the fluorescence provides a means for the detection or quantification of organic compounds when bound to these fluorescent dye compounds. Formula (I), wherein: each of R, R′ and R″ is a hydrogen atom, halogen atom or a straight or branched chain (C1-20alkyl, alkenyl or alkynyl group optionally substituted with one or more halogen, hydroxy and/or oxy group: rings A, B and C optionally include one or more double bonds; rings B and C are optionally substituted with one or more halogen atoms.

Abstract: A process is provided for preparing an enantiopure 1,3-dioxolan-4-one or 1,3-oxathiolan-5-one derivative, which includes bringing a mixture containing enantiomeric 1,3-dioxolan-4-one or 1,3-oxathiolan-5-one derivatives and an enzyme with hydrolytic activity into contact in the presence of a nucleophile. Cleaving a dioxolanone/oxathiolanone ring of one enantiomer occurs by the enzyme with hydrolytic activity and, after the cleavage of one enantiomer has taken place, the uncleaved enantiomer of the 1,3-dioxolan-4-one or 1,3-oxathiolan-5-one derivative is isolated.

Abstract: The invention provides a biosynthetic gene cluster for mitomycin, as well as methods of using gene(s) within the cluster to alter biosynthesis.

Abstract: Recombinant host cells of the suborder Cystobacterineae containing recombinant expression vectors that encode heterologous PKS genes can produce polyketides synthesized by the PKS enzymes encoded on those vectors at high levels.

Abstract: A process for the isolation of clavulanic acid and pharmaceutically acceptable salts thereof, such as potassium clavulanate, from the aqueous fermentation broth of a clavulanic acid-producing microorganism comprises the microfiltration of the broth without prior treatment.

Abstract: The present invention relates to novel bacterial strains useful for the production of 2-keto-L-gulonic acid. The present invention further relates to the use of these strains for the production of 2-keto-L-gulonic acid by fermentative conversion of L-sorbose. The present invention further relates to the use of these novel bacterial strains for the production of pyrroloquinoline quinone and a nontoxic lipopolysaccharide. Also described is the strains of the present invention transformed by a vector.

Abstract: The invention provides new substantially pure antibiotics designated AC-98-1, AC-98-2, AC-98-3, AC-98-4 and AC-98-5 derived from the microorganism Streptomyces hygroscopicus.

Abstract: There is provided a novel method for producing an optically active (4R)-1,3-thiazolidine-4-carboxylic acid by allowing cells of a microorganism or a preparation obtained from cells of a microorganism having activity for stereoselectively hydrolyzing an optically active (4R)-1,3-thiazolidine-4-carboxylic acid amide to act on a mixture of (4R)- and (4S)-enantiomers of a 1,3-thiazolidine-4-carboxylic acid amide to produce the optically active (4R)-1,3-thiazolidine-4-carboxylic acid and separating the optically active (4R)-1,3-thiazolidine-4-carboxylic acid.

Abstract: Novel bacterial genes, microorganisms and processes for improving the manufacture of 5R clavams, eg. clavulanic acid.

Abstract: The present invention relates to novel bacterial strains useful for the production of 2-keto-L-gulonic acid. The present invention further relates to the use of these strains for the production of 2-keto-L-gulonic acid by fermentative conversion of L-sorbose. The present invention further relates to the use of these novel bacterial strains for the production of pyrroloquinoline quinone and a nontoxic lipopolysaccharide. Also described is the strains of the present invention transformed by a vector.

Abstract: The present invention relates to novel substance having inhibitory action on cholesteryl ester transfer protein, WK-5344A substance and WK-5344B substance, and process for production thereof. A microorganism belonging to genus Streptomyces having ability to produce WK-5344A substance and WK-5344B substance is cultured in a medium, and the WK-5344A substance and the WK-5344B substance are accumulated in the medium, then the WK-5344A substance and the WK-5344B substance are isolated from the said medium. Since the present substance shows significant inhibitory action on cholesteryl ester transfer protein, the substance is effective for prevention and treatment of diseases caused by accumulation of cholesterol in human.

Abstract: The present invention relates to novel bacterial strains useful for the production of 2-keto-L-gulonic acid. The present invention further relates to the use of these strains for the production of 2-keto-L-gulonic acid by fermentative conversion of L-sorbose. The present invention further relates to the use of these novel bacterial strains for the production of pyrroloquinoline quinone and a nontoxic lipopolysaccharide. Also described is the strains of the present invention transformed by a vector.

Abstract: The invention relates to a new process for concentrating epothilones in culture media, a new process for the production of epothilones, a new process for separating epothilones A and B and a new strain obtained by mutagenesis for the production of epothilones, as well as aspects related thereto. New crystal forms of epothilone B are also described.

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-thienylsulfanyl) 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.

Abstract: The present invention is to obtain novel FT-0554 substance which is useful for treatment of helminthiasis.

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: Desoxyepothilone compounds are produced by fermentation of an epothilone producing microorganism in the presence of a P450 enzyme inhibitor.

Abstract: The present invention relates to microbial processes for carrying out the asymmetric reduction of a ketone to an alcohol, which comprises: contacting the ketone with a microorganism, or an enzyme reduction system capable of accomplishing the subject reduction comprising an enzyme derived from said microorganism and a co-factor for said enzyme, and incubating the resulting mixture under conditions sufficient to yield more of the desired (R)-enantiomer of the corresponding alcohol than the undesired (S)-enantiomer. The chiral (R)-enantiomer can be used in the synthesis of certain &bgr;-adrenergic receptor agonists.

Abstract: The present invention relates to the production process of biotin by fermentation using a genetically engineered microorganism, and DNA sequences and vectors to be used in such process.

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 present invention provides structure-based combinatorial libraries of compounds containing the functional group minima of picornaviruses including poliovirus and rhinovirus. The libraries can be used to screen for therapeutical antiviral compounds, e.g., anti-picornaviral capsid-binding compounds.

Abstract: The present invention relates to compounds made by a subset of modules from one or more polyketide synthase (“PKS”) genes that are used as starting material in the chemical synthesis of novel molecules, particularly naturally occurring polyketides or derivatives thereof. The biologically derived intermediates (“bio-intermediates”) generally represent particularly difficult compounds to synthesize using traditional chemical approaches due to one or more stereocenters. In one aspect of the invention, an intermediate in the synthesis of epothilone is provided that feeds into the synthetic protocol of Danishefsky and co-workers. In another aspect of the invention, intermediates in the synthesis of discodermolide are provided that feed into the synthetic protocol of Smith and co-workers.

Abstract: The invention relates to a new process for concentrating epothilones in culture media, a new process for the production of epothilones, a new process for separating epothilones A and B and a new strain obtained by mutagenesis for the production of epothilones, as well as aspects related thereto. New crystal forms of epothilone B are also described.

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: Spirolaxine, the compound of formula (I) wherein R is H, and the novel compounds of formula (I) wherein R is (C1-C5) alkyl or CH3(CH2)nCO and n is 1, 2, 3 or 4 are useful in treating gastroduodenal diseases such as gastric ulcers, duodenal ulcers and gastric cancer caused by Helicobacter pylori. Spirolaxine and spirolaxine methyl ether are isolated from the fermentation of Sporotrichum pruinosum ATCC 74278. Spirolaxine and the compounds of formula (I) are also useful in combination with H2 antagonist, colloidal bismuth subcitrate and other antibiotics.

Abstract: The present invention relates to processes for the microbial oxidation of 2-methylquinoxaline to 2-quinoxalinecarboxylic acid which comprise contacting 2-methylquinoxaline with a microorganism, or a suitable mutant thereof, and incubating the resulting mixture under conditions sufficient to yield an amount of said 2-quinoxalinecarboxylic acid. The present processes optionally further comprise the isolation and purification of 2-quinoxalinecarboxylic acid.

Abstract: DNA comprising a regulatory gene for clavulanic acid biosynthesis. DNA is no greater than 7 kb in length and has the configuration of restriction sites shown in FIG. 1 or a fragment thereof. Use of DNA in a method for producing clavulanic acid in a host.