Abstract: A process for the production of clavulanic acid and pharmaceutically acceptable salts thereof by

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: 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 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 polynucleotide molecules comprising nucleotide sequences encoding an aveC gene product, which polynucleotide molecules can be used to alter the ratio or amount of class 2:1 avermectins produced in fermentation cultures of S. avermitilis. The present invention further relates to vectors, host cells, and mutant strains of S. avermitilis in which the aveC gene has been inactivated, or mutated so as to change the ratio or amount of class 2:1 avermectins produced.

Abstract: Improved methods for the preparation of clavams by fermentation of a clavam-producing organism in a suitable medium wherein the ammonium levels are kept low so as to avoid repression of enzymes, particularly urease, are disclosed.

Abstract: The present invention relates especially to a DNA fragment that is obtainable from the gene cluster within the genome of Streptomyces or Actinomyces that is responsible for staurosporin biosynthesis and that contains at least one gene or a part of a gene that codes for a polypeptide that is involved directly or indirectly in the biosynthesis of staurosporin and to methods of preparing said DNA fragment. The present invention relates furthermore to recombinant DNA molecules containing one of the DNA fragments according to the invention and to the plasmids and vectors derived therefrom. Also included are host organisms transformed with the said plasmid or vector DNA.

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: 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 producing a compound of the general formula (I): (wherein R1 represents hydrogen, a lower alkanoyl group or a lower alkyl group; R2 and R3each represents hydrogen or a lower alkanoyl group) characterized in that a compound of the general formula (II): (wherein R1, R2 and R3 are respectively as defined above) is reacted with a culture of a strain of microorganism belonging to the genus Fusarium or its cells harvested by filtering the broth.

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: to a process for their production, to a pharmaceutical composition containing the same and to a use thereof.

Abstract: This invention provides a process for producing a macrocyclic lactone compound, which comprises cultivating Actinoplanes sp. FERM BP-3832, in the presence of L-proline, L-hydroxyproline or L-nipecotic acid, and then isolating a macrocylic lactone compound from the fermentation broth. The compounds produced by this process include a compound of the following formula: The present invention also relates to a pharmaceutical composition comprising the same, which is useful as immunosuppressive, antimycotic, antitumor agent or the like.

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: The subject invention pertains to a process for preparing a compound having a formula (4) or (5), in either optically-enriched or racemic form, wherein R1, R2, R3 and R4 are independently selected from hydrogen, alkyl, aryl, alkaryl, aralkyl and acyl groups. In one embodiment, the process of the invention comprises mixing with a plant extract obtained from crushed daffodil bulbs or crushed snowdrop bulbs an oxidative cyclisation precursor of the compound.

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: Cis- and trans-pyrrolopiperidines are advantageously separated into their optical isomers when monoacylating by enzymatic process a mixture containing (R,R)- and (S,S)-pyrrolopiperidine or (S,R)- and (R,S)-pyrrolopiperidine, thereby obtaining a mixture (I) containing (R,R)- and (S,S)-6-acyl-pyrrolopiperidine or (S,R)- and (R,S)-6-acyl-pyrrolopiperidine. Said mixture (I) is then again acylated by enzymatic process, thereby obtaining a mixture (II) containing (S,S)-1,6-diacyl- and (R,R)-6-acyl-pyrrolipiperidine or (S,R)-1,6-diacyl- and (R,S)-6-acyl-pyrrolopiperidine; the enzyme and optionally the solvent and the excess acylating agent are separated from the mixture (II), and the rest is treated with aqueous acid, and the (S,S)-1,6-diacyl-pyrrolopiperidine or the (S,R)-1,6-diacyl-pyrrolopiperidine is separated by extraction and the extraction residue is alkalinized, and the (R,R)-6-acyl-pyrrolopiperidine or the (R,S)-6-acyl-pyrrolopiperidine is separated by extraction.

Abstract: A process for the recovery of natamycin from a fermentation broth containing biomass and natamycin, which comprises:(a) disintegrating the biomass; and(b) separating the natamycin from the thus treated fermentation broth.

Abstract: Colchicinoid compounds are transformed into the corresponding 3-O-glycosyl derivatives by means of Bacillus megaterium strains.

Abstract: Methods are provided for improving the microbial production of amphotericin B by the selective inhibition of amphotericin A by means of protein synthesis inhibitors.

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: This invention relates to Streptomyces avermitilis lacking branched-chain amino acid transaminase activity, branched-chain 2-oxo acid biosynthetic activity and, optionally and preferably, avermectin B-O-methyl transferase activity, methods for preparation thereof, and use thereof to produce natural and non-natural avermectins from branched-chain fatty acid or branched-chain 2-oxo acid precursors. Such avermectins are useful as parasiticides.

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: The invention generally provides the genes of the biotin biosynthetic operon of Bacillus subtilis, and closely related species thereof, and well as constructions useful for high level production of biotin.

Abstract: Disclosed are the novel C-glycoside compounds Mer-1020dA, Mer-1020dB, Mer-1020dC and Mer-1020dD which have a chromophore group in common with well-known chrysomycins A and B, but can be distinguished from the chrysomycins and the like in that the novel C-glycoside compounds have a sugar residue having a higher degree of oxidation, as well as the compound Mer-1020dE comprising only the chromophore thereof. Among these compounds, the C-glycoside compounds are antibiotics which have low toxicity and can strongly inhibit the growth of solid cancer cells in particular.

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 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: The present invention provides a purification process of K-252a, which comprises:treating microorganism cells containing K-252a represented by formula (I): ##STR1## with an alkaline solution to convert K-252a into K-252b represented by formula (II): ##STR2## or alkali salts thereof, which are then released out of the cells, methylating K-252b or alkali salts thereof to convert them into K-252a again, andisolating and collecting the resulting K-252a.

Abstract: Improved methods for the preparation of clavams by fermentation of a clavam-producing organism in a suitable medium wherein the ammonium levels are kept low so as to avoid repression of enzymes, particularly urease, are disclosed.

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: Disclosed is a method for producing folic acid, comprising incubating yeast having the ability to produce folic acid of 0.3 mg or more or incubating bacteria having the ability to produce folic acid of 1 mg or more per liter of the culture, thereby accumulating folic acid in the culture.

Abstract: The present invention relates to chrolactomycin compound represented by the following formula (I): ##STR1## or pharmaceutically acceptable salts thereof having antibacterial and antitumor activities.

Abstract: An acidic polycyclic ether antibiotic, having structure established by X-ray crystallography, is formed by fermentation of a novel microorganism, Streptomyces sp. ATCC 55028. This novel antibiotic is useful as an anticoccidial in chickens, in the prevention or treatment of swine dysentery, as a growth promotant in cattle and swine, and as an anthelmintic in mammals, particularly in dogs, cats, sheep, cattle and swine.

Abstract: Conjugates of chlorophyll (Chl) and bacteriochlorophyll (Bchl) derivatives with amino acids, peptides and proteins are provided by the invention. The amino acid, peptide or protein residue is linked to the 17-propionic acid group of a Chl or Bchl residue directly or through a chain. The conjugates are for use as photosensitizers in photodynamic therapy and in diagnostics of tumors. Conjugation with cell-specific ligands, such as hormones, growth factors or tumor-specific antibodies, will target the Chl or Bchl moiety to the tumor site. Thus, conjugates with melanocyte stimulating hormones are suitable for photodynamic therapy of melanoma tumors.

Abstract: A process for producing d-biotin comprises cultivating a microorganism of the genus Kurthia and which is resistant to biotin antimetabolites and capable of producing d-biotin in a medium under aerobic conditions, and separating the resulting d-biotin from the fermentation broth. The cultivation medium suitably contains an assimilable carbon source, a digestible nitrogen source, inorganic salts and other nutrients necessary for the growth of the microorganism at a pH of about 5-9, temperature of about 10-40.degree. C. and for a duration of about 1-10 days. The preferred microorganism are Kurthia sp. 538-KA26, 538-17H4, 538-51F9 and 538-2A 13 (DSM No. 10609, 10608, 10610 and 10607, respectively), which are also new, and as such represent a further aspect of the present invention. The so-produced d-biotin is one of the essential vitamins for the nutrition of animals, plants and microorganisms, and is important as a medicine or food additive.

Abstract: A process for separating a natural B avermectin from a natural avermectin containing fermentation broth by using an aqueous precipitation. The process comprises extracting natural avermectins from the fermentation broth with a water miscible solvent and adding sufficient water to precipitate the natural B avermetins. Preferably, the water miscible solvent is a C.sub.1 -C.sub.3 alcohol, acetone, or acetonitrile. In addition, an acid, base, salt or surfactant may be added to facilitate the precipitation. This invention provides an isolation technique that substitutes the use of an aqueous precipitation for nonaqueous solvent precipitations. The reduction in use of nonaqueous solvents provides economic, environmental and safety benefits.

Abstract: Natamycin biomass comprising 5-60% natamycin, most preferably 25-60% natamycin, and methods for forming the biomass, are disclosed. The natamycin biomass can be mixed with compatible carrier to form a premix comprising 0.2-5% natamycin. The premlix may be mixed with animal feed to form an animal feed mixture comprising cracked grain and 1.1-110 ppm of natamycin.

Abstract: A compound of the formula (I): ##STR1## or a pharmaceutically acceptable salt, or a hydrate thereof, a process for preparing said compound, and a pharmaceutical composition having antiviral activity which comprise said compound.

Abstract: This invention relates to glycosyltransferase, genes encoding glycosyltransferase, recombinant vectors having such a gene, host cells transformed with such a recombinant vector, and uses thereof. This invention makes it possible to glycosylate indolopyrrolocarbazole derivatives conveniently and economically.

Abstract: Coal is treated aerobically or anaerobically to produce humic acid, volatile fatty acids, lower alcohols, and/or methane using a consortium of bacteria designated Mic-1 or KSARC56. This process can also be used to convert aromatic compounds, such as phenols and derivatives thereof, to methane and carbon dioxide.

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: Process and novel intermediates for preparing the mono-L-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol ganciclovir) and its pharmaceutically acceptable salts. The present process and monoester intermediates provide for mono-esterification by an L-valine derivative, resulting in a monocarboxylate-monovalinate which is then selectively hydrolyzed under basic or enzymatic conditions to give the monovaline ester of ganciclovir in high yield and purity. These products are of value as antiviral agents with improved absorption.

Abstract: The invention is directed to a compound of formula ##STR1## in which R represents a hydroxyl, alkyloxy, phenylalkyloxy or --NH--CH.sub.2 --COOH radical, R.sub.1 represents a hydrogen atom, an adamantylacetyl, adamantylcarbonyl, norbornylacetyl, norbornylphenoxycarbonyl, benzoyl, nicotinoyl, 4-phenylbenzoyl, 4-tert-butylbenzoyl or 2-pyrrolidinecarbonyl radical or a protective group for an amine functional group, R.sub.2 represents an Arg or Lys residue, R.sub.3 represents an Arg or Lys residue, R.sub.4 represents a Pro residue, m, n and p, which are the identical or different, represent a number equal to 0 or 1, R.sub.5 and R.sub.6 are identical and represent a hydroxyl or methoxy radical and R.sub.7 represents a hydrogen, chlorine, bromine or iodine atom or a nitro radical, or the compound wherein one or a number of peptide bonds between two amino acid residues are replaced by --CH.sub.2 --NH bonds or the peptide bond between the R.sub.2 and R.sub.3 amino acid residues is replaced by a CH.dbd.

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 FO-1289 substance of the formula ##STR1## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are hydrogen or acyl. A process for the production thereof comprises culturing the novel microorganism Aspergillus sp. FO-1289 FERM BP-4242 in a nutrient medium, accumulating the FO-1289 substance thus produced in the medium, and isolating the FO-1289 substance therefrom. Particular species of the FO-1289 substance comprise FO-1289A, in which R.sub.1, R.sub.2 and R.sub.3 are acetyl and R.sub.4 is hydrogen; FO-1289B, wherein R.sub.1 is propionyl, R.sub.2 and R.sub.3 are acetyl and R.sub.4 is hydrogen; FO-1289C, wherein R.sub.1 and R.sub.3 are acetyl, R.sub.2 is propionyl and R.sub.4 is hydrogen; and FO-1289D, wherein R.sub.1 and R.sub.2 are acetyl, R.sub.3 is propionyl and R.sub.4 is hydrogen.

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: UCS1025 compounds represented by the following formula (I): ##STR1## wherein R represents hydrogen or hydroxyl group, or tautomers or pharmacologically acceptable salts thereof.

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: 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: This invention relates to glycosyltransferase, genes encoding glycosyltransferase, recombinant vectors having such a gene, host cells transformed with such a recombinant vector, and uses thereof. This invention makes it possible to glycosylate indolopyrrolocarbazole derivatives conveniently and economically.