Abstract: Modified PKS gene clusters which produce novel polyketides in an efficient system in a host cell or in a cell free extract are described.

Abstract: The present invention concerns an enzymatic oxidative deamination process of a dipeptide monomer to prepare an intermediate useful to prepare compounds having endopeptidase and angiotensin converting enzyme inhibition activity.

Abstract: A process for preparing enantiomerically pure alcohols of the formula I (Ia or Ib) where the substituents have the following meanings: R1 hydrogen or substituted or unsubstituted C1-C6-alkyl, C1-C6-alkoxy or C1-C6-alkanoyl, R2 and R3 independently of one another hydrogen or substituted or unsubstituted C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkanoyl, C1-C6-alkylthio, C1-C6-alkylsulfinyl or C1-C6-alkylsulfonyl, R4 substituted or unsubstituted C1-C6-alkyl, C3-C8-cycloalkyl, which comprises reducing compounds of the formula II where the substituents R1 to R4 have the abovementioned meanings  in aqueous solution in the presence of a carbon source and of a microorganism or of a reducing agent, of a cofactor and of an enzyme, to compounds of the formula I.

Abstract: The present invention discloses the use, in the manufacture of a preventive and therapeutic drug of a brain disease, of a compound represented by formula (1): CH2═CH—CH2—S(O)n—R  (1) [wherein R represents a hydrogen atom, an alkyl group, an alkenyl group, a substituted alkyl group, a substituted alkenyl group, an alkylthio group, an alkenylthio group, a phenyl group, a substituted phenyl group, a heterocyclic group, or a group derived from an amino acid or an oligopeptide by deletion of one hydrogen atom, and which group may have a protective group; and n is 0, 1, or 2], a glycoside thereof, or a salt of the compound or the glycoside. The drug of the present invention for ameliorating brain diseases, inhibiting reduction of brain neurons and promoting branching of neurites, is useful for the prevention and treatment of brain diseases such as dementia in association with degeneration and sloughing of brain neurons.

Abstract: This invention relates to crystalline pharmaceutically acceptable salts of an alpha 1a adrenergic receptor antagonist, Compound A, which are useful in the treatment of benign prostatic hyperplasia. Pharmaceutical compositions employing the crystalline salts, and processes for making and using the crystalline salts and pharmaceutical compositions of Compound A are also disclosed. This invention further relates to a process for obtaining enantiomerically pure intermediate useful for the synthesis of end product alpha 1a adrenergic receptor antagonists. The end product compounds are useful for the treatment of benign prostatic hyperplasia and for relaxing lower urinary tract tissue. The invention also relates to a process for preparing a class of dihydropyrimidinone compounds of which Compound A is a member, wherein the process involves deprotonating a dihydropyrimidinone compound and then coupling the deprotonated derivative with a primary amine.

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 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: Methods and novel intermediates of the formula: wherein R6 and R7 are lower alkyl or benzyl or R6 and R7 taken together are —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2CH2—, R8 is C1-C21 alkyl or a C2-C21 monounsaturated alkenyl, which may optionally be substituted with substitution substituents independently selected from the group consisting of hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy C1-C6 alkyl, C1-C6 alkanoyl, amino, halo, cyano, azido, oxo, mercapto and nitro, and R9 is an alcohol protecting group. The intermediates are useful for the preparation of acyclic nucleoside derivatives of the formula: where one of R1 and R2 is an amino acid acyl group and the other of R1 and R2 is a —C(O)C3-C21 saturated or monounsaturated, optionally substituted alkyl and R3 is OH or H; or a pharmaceutically acceptable salt thereof.

Abstract: Spirolaxine, the compound of formula (I) wherein R is H, and the novel compounds of formula (I) wherein R is (C1-C6)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 invention relates to biologically active novel compounds having formula (I) as defined herein. Also disclosed are methods of preparing said compounds, fungicidal compositions comprising, as an active ingredient, these compounds, use of the compounds, and method of controlling fungi at loci infested or liable to be infested therewith.

Abstract: The present invention relates to a process for producing a xanthine derivative represented by formula (II), comprising converting a xanthine derivative represented by formula (I) {hereinafter, referred to as Compound (I)}: ##STR1## (wherein R.sup.1 and R.sup.2 independently represent hydrogen, or hydroxy-substituted, oxo-substituted, or unsubstituted lower alkyl) into a xanthine derivative represented by formula (II) {hereinafter, referred to as Compound (II)}: ##STR2## (wherein R.sup.3 and R.sup.4 independently represent hydrogen, or hydroxy-substituted, oxo-substituted, or unsubstituted lower alkyl; R.sup.5 and R.sup.6 independently represent hydrogen, hydroxy, or oxo; with the proviso that R.sup.5 and R.sup.6 are both hydrogen, at least one of R.sup.3 and R.sup.

Abstract: A batch fermentation is carried out continuously or semicontinuously using strain of Streptomyces clavuligerus for the production of clavulanic acid. The fermentation process is carried out with strict control of the soluble phosphate in the medium both at the beginning and throughout the process.

Abstract: A process for preparing a compound of Formula (3) in which R.sup.2 is --H; ##STR1## which comprises the steps: i) conversion of a compound of Formula (1) into a compound of Formula (2) using a dioxygenase enzyme; ##STR2## ii) conversion of the compound of Formula (2) into a compound of Formula (3) wherein is --COR; andiii) conversion of the compound of Formula (3) in which R.sup.2 is --COR into a compound of Formula (3) in which R.sup.2 is --H;wherein R.sup.2, a, b, c, d, Z, m and X are as defined in claim 1.Also claimed are individual steps of the process and new compounds of Formula (2).

Abstract: A microorganism resistant to a threonine analogue, which has a plasmid containing part or whole of a biotin operon; and a process for producing biotin, which comprises culturing a microorganism described above in a medium to produce and accumulate biotin in the medium, and collecting biotin.

Abstract: An imperfect fungus such as a microorganism belonging to the genus Curvularia in a culture medium containing nutrients utilizable for normal microorganisms and isolating MK7634 substance of a molecular formula: C.sub.8 H.sub.15 N.sub.3 O.sub.4 from the culture by, for example, solvent extraction, ion exchange resin technique or gel filtration chromatography. The MK7634 substance can be used as an active ingredient of drugs. In particular, the MK7634 substance is a novel anthelmintic substance and expected to be used as an active ingredient of anthelmintics.

Abstract: Exochelins can be used to prevent damage to organs for transplant from the formation or presence of the .circle-solid.OH radical. In particular, the invention is directed to the administration of exochelins to the organ prior to or coincidental with removal from a donor, storage, implantation in a recipient or in conjunction with reestablishment of flow of body fluids to the organ.

Abstract: A process is described for preparing a compound of the formula or the S-enantiomer thereof,wherein:R is alkyl, aryl, cycloalkyl, aralkyl, or cycloalkylalkyl,R.sup.1 is halogen;R.sup.2 is halogen, alkyl, cycloalkyl, aryl or ##STR1## wherein the process comprises treating the associated racemic alcohol with an acylatingagent ##STR2## (wherein L is a leaving group) and an enzyme or microorganism capable of enantioselective acylation. This process may also be used to isolate the unreacted R- or S-alcohol. The acylated product may be enantioselectively hydrolyzed with a lipase or lipase-supplying microorganism to the S- or R-alcohol. Compounds prepared by this invention are useful antipsychotic agents or useful intermediates therefor.

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

Abstract: The disclosure concerns a process for the microbial preparation of riboflavin by culturing riboflavin-producing microorganisms in a nutrient medium and then isolating the riboflavin which has been produced, which comprises using microorganisms in which the endogenous isocitrate lyase (ICL) activity has been altered.

Abstract: Novel compounds isolated from the fermentation of producing cultures of Nodulisporium sp. are antiparasitic and insecticidal agents.

Abstract: The present invention relates to the novel antitumor antibiotic designated BMS-199687 and to its preparation. The compound is obtained by culturing a new strain of Actinomadura ferruginea. BMS-199687 demonstrates antitumor activity in standard antitumor animal model systems.

Abstract: This invention relates to a new biologically active compound as shown in formula (I) and its biologically active derivatives; whereas derivatives are produced by the reaction of formula (I) with nucleophiles.

Abstract: Disclosed are novel antifungal agents having the formula: ##STR1## as well as a pharmaceutically acceptable salt, ester of prodrug thereof, whereinR is: ##STR2## --C(O)--R.sub.1 wherein R.sub.1 is alkyl, alkenyl, aryl, arylalkenyl, aryl-aryl-, arylalkoxy-aryl-, aryl-aryl-aryl-, arylkoxy-aryl-aryl-, or ##STR3## wherein R.sub.2 is alkylamino, dialkylamino, (heterocyclic)alkyl, aryl, or arylalkyl; andX is O, NH, or NR.sub.3 wherein R.sub.3 is alkyl or aryl. Also disclosed are pharmaceutical compositions comprising a compound of the invention in combination with a pharmaceutically acceptable carrier; and a process for preparing the compounds of the invention.

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: This invention provides processes for producing phthalide compounds which comprise cultivating Phanerochaete avelutina FERM BP-4787 and then isolating phthalide compounds from the fermentation broth.

Abstract: 1. WF16616 substance represented by the following structural formula (1) or its pharmaceutically acceptable salt. ##STR1## WF16616 substance exhibits an antimicrobial activity, especially an excellent antifungal activity.

Abstract: A method for producing lysocellin in bead form comprises:(a) cultivating a lysocellin-producing microorganism in an aqueous nutrient-containing fermentation broth under lysocellin-producing conditions;(b) adding a base or inorganic phosphate to the fermentation broth within about the first 24 hours of the beginning of the fermentation in an amount sufficient to ensure that the lysocellin is produced in the form of a cation salt of lysocellin;(c) providing a lipid to the fermentation broth such that the lipid is present in the broth in a sufficient amount to form discrete beads with the lysocellin in the fermentation broth; and(d) separating the beads from the broth.

Abstract: Enantiomeric or enantiomerically enriched H.sup.+ K.sup.+ ATPase inhibiting pyridinylsulfinyl--benzimidazoles are prepared using microorganisms or microbial enzyme systems to enantioselectively biooxidize corresponding prochiral sulfide compounds and isolating the pharmaceutically active enantiomer or enantiomerically enriched sulfoxide form.

Abstract: The invention is directed toward the use of desferri-Exochelins to destroy cancer cells or retard or eliminate the growth of those cancer cells.

Abstract: Novel compounds isolated from the fermentation of producing cultures of Nodulisporium sp. are antiparasitic and insecticidal agents.

Abstract: This invention relates to tricyclo compounds useful for treatment and prevention of resistance by transplantation, graft-versus-host diseases by medulla ossium transplantation, autoimmune diseases, infectious diseases, and the like, which can be represented by the following formula: ##STR1## to a process for their production, to a pharmaceutical composition containing the same and to a use thereof.

Abstract: A process for the resolution of a racemic mixture of nucleoside enantiomers that includes the step of exposing the racemic mixture to an enzyme that preferentially catalyzes a reaction in one of the enantiomers. The nucleoside enantiomer (-)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane is an effective antiviral agent against HIV, HBV, and other viruses replicating in a similar manner. In particular, deaminase, PPL, PLE and subtilisn are used to resolve 1,3-oxathiolane nucleoside enantiomers.

Abstract: The present invention is directed to a process for improving the property of proanthocyanidins comprising contacting the proanthocyanidin containing solution with tannase and a process for increasing the yield of proanthocyanidins comprising contacting the proanthocyanidin containing solution with tannase in the extraction of the proanthocyanidins.

Abstract: The present invention relates to the novel antitumor antibiotic designated BMS-199687 and to its preparation. The compound is obtained by culturing a new strain of Actinomadura ferruginea. BMS-199687 demonstrates antitumor activity in standard antitumor animal model systems.

Abstract: This invention provides compounds of the following chemical formula or their pharmaceutically-acceptable salts: ##STR1## wherein R is hydrogen or chloro. Also, the present invention provides a process for the production of the compound of formula I, which comprises cultivating a microorganism having the identifying characteristics of Aspergillus fischeri var. thermomutatis ATCC 18618 or the like, and then isolating the compound of formula I from the fermentation broth. The pyrrolobenzoxazine compounds of formula I of this invention have broad antiparasitic activity, and thus are useful as antiparasitic agents, especially as anthelmintics.

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. Additional steps may include an optional ultrafiltration of the microfiltration filtrate, concentration of the filtrate, direct extraction of the concentrated filtrate with a water-immiscible organic solvent, washing, drying, and concentration of the organic solvent, and isolation of the clavulanic acid or a pharmaceutically acceptable salt from the organic solvent.

Abstract: There are disclosed 18-thiomarcfortine derivatives of the natural products marcfortine A, B and C, C-18 thioparaherquamide and derivatives thereof, novel N-1 marcfortines A, B, and C and derivatives thereof, novel N-1 paraherquamide and derivatives thereof usefull in the treatment and prevention of helninth and arthropod infections of animals and plants.Any inquiry concerning this communication or earlier communications from the examiner should be directed to Examiner Robert T. Bond whose telephone number is (703)308-4711. The examiner can normally be reached on Monday through Friday from 8:00 AM to 4:30 PM.

Abstract: The present invention aims at enhancing purity of the proanthocyanidin extracts by acting yeast to the proanthocyanidin extracts for fermenting them to thereby assimilate the impurities such as saccharides with yeast to reduce them.

Abstract: The antibiotic aflastatin A or its salt and its production by Streptomyces sp. MRI 142, FERM BP-5841 is presented. Aflastatin A is incorporated into a pharmaceutical composition and is employed as an aflatoxin contamination inhibitor, antimicrobial agent, antifungal agent and antitumor agent.

Abstract: Bioactive substances K93-0711 I-1 and I-2 having inhibitory action on IL-6 activity, are produced by culturing a microorganism belonging to the genus Streptomyces in a medium, whereby the bioactive substances K93-0711 I-1 and I-2 accumulate in the medium. These bioactive substances K93-0711 I-1 and I-2 are then isolated therefrom. The substances are effective for treatment of IL-6-involving diseases such as cancer cachexia, multiple myeloma and rheumatoid arthritis.

Abstract: A process for the biotechnological preparation of alcohols, aldehydes and carboxylic acids by oxidation of compounds of the formula R.sup.1 --C(CH.sub.3).dbd.CR.sup.2 R.sup.3, where R.sup.1, R.sup.2 and R.sup.3 have the meanings indicated in the description, with the aid of microorganisms is described.

Abstract: A process for the resolution of a racemic mixture of nucleoside enantiomers that includes the step of exposing the racemic mixture to an enzyme that preferentially catalyzes a reaction in one of the enantiomers. The nucleoside enantiomer (-)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane is an effective antiviral agent against HIV, HBV, and other viruses replicating in a similar manner.

Abstract: A process for the production of an extracellular peroxidase using confectionery waste is disclosed. The first step of the process requires culturing a piece of plant tissue containing extracellular peroxidase-producing cells from a plant of the genus Acer, more specifically Acer pseudoplantanus. The culture medium is a solid culture medium and the culturing step is carried out until a callus forms on the solid culture medium. Further, the plant cells produced in the callus are dispersed into a liquid culture medium to form a suspension of plant cell culture. The suspension culture medium contains confectionery waste products which provide 1 to 15% by weight of sugars (i.e. fructose, glucose and sucrose). The culturing of the plant cells in suspension in the liquid culture medium with the concomitant accumulation of the extracellular peroxidase in the liquid culture medium and separating the enzyme therefrom.

Abstract: A process for preparing 5-(4-?2-(N-methyl-N-(2-pyridyl)amino)-ethoxy!-benzyl)-2,4-thiazolidinedion e, by treating 5-(4-?2-(N-methyl-N-(2-pyridyl)amino)-ethoxy!benzylidene)-2,4-thiazolidine dione with a free whole yeast cell culture or immobilized whole yeast cells from Rhodotorula glutinis CBS 4406 or Rhodotorula rubra CBS 6469 as the microbial reductase source and recovering 5-(4-?2-N-methyl-(N-(2-pyridyl)amino)ethoxy!-benzyl)-2,4-thiazolidinedione , or a salt thereof.

Abstract: Exochelins can be used to prevent damage to living tissue from the formation or presence of the (.cndot.OH) radical. In particular, the invention is directed to the administration of exochelins to infarcted myocardium prior to or coincidental with reperfusion to prevent damage to myocardium from iron mediated free radical formation. Also presented is the chemical structure of exochelins and modified exochelins as well as other applications of these materials in the treatment and diagnosis of disease in mammals.

Abstract: A compound of formula (I) is obtainable by the cultivation of a genus Streptomyces, such as Streptomyces NCIMB 40515. in the presence of rapamycin, and recovery thereof from the culture medium. The compound, and pharmaceutical compositions containing it, is useful as an immunomodulatory agent as an anticancer agent, or in the treatment of microbial infections in animals including humans.

Abstract: There is disclosed a novel compound having the formula ##STR1## which exhibits antifungal activity.

Abstract: The invention is a compound of the formula: ##STR1## wherein M is a bivalent or trivalent metal ion, and X is OH or O.sup..crclbar.. The above compound of the present invention is useful for prevention or treatment of mycoplasmosis.

Abstract: There is disclosed a novel compound having the formula ##STR1## which exhibits antifungal activity.

Abstract: A method for the production of indigo and indirubin dyes using a recombinant Escherichia coli containing a gene encoding a phenol hydroxylase from Bacillus stearothermophilus. The dyes are used for coloring cloth and the like.