Abstract: The carE gene of Streptomyces thermotolerans has been isolated and used to construct recombinant DNA expression vectors. The carE gene encodes 4"-O-isovaleryl acylase activity important in the biosynthesis of a number of useful antibiotics. The carE gene can be used not only to construct recombinant cells with an increased ability to produce the acylase enzyme but also to construct recombinant cells with the ability to produce novel antibiotic compounds.
Abstract: Disclosed are DC115A compounds represented by the following general formula: ##STR1## wherein R represents ethyl, propyl or 1-propenyl, and which have antibacterial and anti-tumor activity. DC115A compounds are produced by culturing a microorganism belonging to the genus Streptomyces.
Abstract: The present invention discloses a method for producing a novel antibiotic, 2"'-O-demethyltylosin. The novel antibiotic, utilizing recombinant DNA technology, can be produced from a transformed mutant of a tylosin producing microorganism. By transforming for example Streptomyces fradiae GS 16 with plasmid pHJL284, the transformant can produce 2"'-O-demethyltylosin. Streytomyces fradiae GS16 is a tylosin producing species that contain a mutation in the tylE gene found in the tylosin biosynthetic pathway. The tylE gene codes for demethylmacrocin 2"'-O-methyltransferase enzyme (DMOMT), the enzyme that methylates the 2-hydroxyl position of the 6-deoxyallose moiety. Plasmid pHJL284 contains the cloned tylF gene which codes for the macrocin 3"'-O-methyltransferase enzxyme (MOMT), the enzyme that methylates the 3"'-hydroxyl position, but it does not contain the tylE gene. Transformation of S.
Type:
Grant
Filed:
March 28, 1988
Date of Patent:
November 5, 1991
Assignee:
Eli Lilly and Company
Inventors:
Karen L. Cox, Eugene T. Seno, Gene M. Wild
Abstract: A novel gene conferring resistance to picromycin in Streptomyces and related organisms was cloned from a genomic library of Streptomyces felleus DNA. The novel picromycin resistance-conferring gene can be isolated on an .about.2.8 kb PvuII fragment by subcloning the restriction fragment from plasmid pOJ321. This PvuII fragment contains all of the information required for the expression of the picromycin resistant phenotype in Streptomyces. Methods for inducing resistance, as well as vectors and transformants containing the novel picromycin resistance gene, are provided.
Abstract: High titers of polyether antibiotics are obtained in a fermentation broth by inoculating a nutrient fermentation broth with a microorganism capable of producing a polyether antibiotic. Growth of the microorganism is established in the broth by incubating the inoculated broth at a physiologically acceptable temperature until pH of the broth begins to rise upon establishment of growth of the microorganism. A free fatty acid then is fed into the broth to achieve and maintain a free fatty acid concentration in the broth of about 0.1% by weight or greater but less than a level at which the free fatty acid is toxic to the microorganism. The free fatty acid is fed into the broth during the remainder of fermentation at about a rate at which the free fatty acid is consumed by the microorganism, to product high titers of the polyether antibiotic.
Abstract: An aqueous medium having dispersed therein hydrophobic, polyether antibiotic-containing droplets, is mixed to cause the droplets to collide with each other and coalesce to form agglomerates which are separable from the medium.
Abstract: Xylose isomerase (XI) muteins useful in the conversion of glucose to fructose or xylose to xylulose are obtained in usable amounts by protein structural and recombinant DNA methods, including x-ray crystallography, cloning, computer graphic modeling and site-directed mutagenesis and expression of the bacterial DNA sequences encoding native procaryotic xylose isomerase. These native sequences are altered to encode the xylose isomerase muteins having improved catalytic function and/or thermostability.
Type:
Grant
Filed:
August 11, 1987
Date of Patent:
August 20, 1991
Assignees:
Cetus Corporation, Univerity of Oregon
Inventors:
Robert J. Drummond, Will Bloch, Brian W. Matthews, Pamela L. Toy
Abstract: Polyether antibiotic material is liberated from agglomerates containing a lipid material and the polyether antibiotic material by separating the polyether antibiotic from the lipid through formation of an acid salt of the lipid and a desired acid salt of the polyether antibiotic. The agglomerates can be formed during fermentation or produced by adding lipids afterwards.
Abstract: A novel antibiotic designated BU-4146T is produced by fermentation of Streptomyces amphibiosporus strain R310-104 (ATCC-53964). The antibiotic possesses both antifungal and antitumor activity.
Type:
Grant
Filed:
July 23, 1990
Date of Patent:
August 6, 1991
Assignee:
Bristol-Myers Squibb Company
Inventors:
Masataka Konishi, Koko Sugawara, Masaru Ohbayashi, Takeo Miyaki
Abstract: Antiparasitic milbemycin derivatives having at the C.25 position a substituted 2-propenyl group --C(CH.sub.3).dbd.CH--R.sup.2 wherein R.sup.2 is a C.sub.3 -C.sub.8 alkyl, alkenyl or alkynyl group which may optionally contain an oxygen or sulphur atom as part of the chain, or a C.sub.3 -C.sub.8 cycloalkyl or cycloalkenyl group, or a 3 to 6 membered oxygen or sulphur containing heterocyclic ring which may optionally be substituted by one or more alkyl groups or halogen atoms; and process for their preparation.
Abstract: A culture comprising the microorganism Micromonospora echinospora ssp. calichensis DR46 (ATCC-53591), which produces complementing factor, is described and disclosed.
Type:
Grant
Filed:
March 6, 1987
Date of Patent:
June 18, 1991
Assignee:
American Cyanamid Company
Inventors:
David M. Rothstein, Susan F. Love, Ellen Z. Baum
Abstract: The present invention relates to new WS7622A, B, C and/or D substances, derivatives thereof and pharmaceutical compositions containing the new substances as active ingredients.
Abstract: The compounds of formula I ##STR1## wherein eitherR.sub.1 is hydroxy,R.sub.2 is allyl or n-propyl andthere is a single bond between the carbon atoms numbered 14 and 15orR.sub.1 is missing,R.sub.2 is allyl andthere is a double bond between the carbon atoms numbered 14 and 15,have interesting immunosuppressant and anti-inflammatory properties.They are obtained by fermentation or synthesis, e.g. by hydrogenation or dehydration.
Abstract: Virginiamycin M.sub.1 having the Formula: ##STR1## and virginiamycin M.sub.1 analogs having the Formulae I-IV: ##STR2## Virginiamycin M.sub.1 and the analogs I-IV are antagonists of cholecystokinin (CCK) and gastrin. Cholecystokinin antagonists are useful as analgesics and in the treatment and prevention of disorders of the gastrointestinal, central nervous and appetite regulatory systems in animals, especially humans. Gastrin antagonists are useful in blocking the receptors for gastrin in humans and may function as agents for the treatment of ulcers, tumors or other gastrointestinal disorders. The compounds of Formulae I-IV are antibiotics and are useful as antimicrobial agents in animals including man and are useful as food additives to promote feed utilization in animals. Virginiamycin M.sub.1 and the analogs of Formula I, III and IV are produced by the controlled aerobic fermentation of a strain of Streptomyces olivaceus, ATCC No. 53527, while the analog of Formula II is produced by chemical synthesis.
Type:
Grant
Filed:
October 26, 1989
Date of Patent:
April 9, 1991
Assignee:
Merck & Co., Inc.
Inventors:
Yiu-kuen T. Lam, Otto D. Hensens, Raymond S. Chang, Cheryl D. Schwartz, Deborah L. Zink
Abstract: This invention relates to an antibiotic NK86-0279 of the formula: ##STR1## which exhibits antifungal, antitumor, vascularizations-inhibitory and insecticidal activities.
Abstract: A novel compound, DC-107, is produced by culturing a microorganism belonging to the genus Streptomyces. It is useful as a medicine because of its antibacterial and anti-tumor activity.
Abstract: A process for preparing sorbic acid which comprises treating sorbic aldehyde with at least one microorganism selected from Mycobacterium, Rhodopseudomonas, Streptomyces, Acetobacter, Alcaligenes and Gluconobacter. According to the present invention, sorbic acid can be prepared in high yield by oxidizing sorbic aldehyde with the specific microorganism.
Abstract: An new antibiotic having the chromophore structure of the pluramycin family of antibiotics is produced by fermentation of Streptomyces violaceus ATCC 53807. The new antibiotic designated BU-3839T, exhibits potent antibacterial activity and also inhibits the growth of tumors in experimental animal systems.
Abstract: Oxirane-pseudooligosaccharides of the formula I ##STR1## in which z is zero or 1, their physiologically acceptable salts with acids, a process for their preparation, pharmaceutical preparations, and their use are described. The compounds have an .alpha.-glucosidase-inhibiting action.
Type:
Grant
Filed:
August 11, 1987
Date of Patent:
February 5, 1991
Assignee:
Hoechst Aktiengesellschaft
Inventors:
Laszlo Vertesy, Joachim Betz, Hans-Wolfram Fehlhaber, Karl Geisen
Abstract: Novel azoxy compounds having antifungal activity and being useful for the treatment of mycoses, represented by the following formula ##STR1## are prepared by culturing a microorganism of Streptomyces sp. (KC-7367, FERM BP-1277) and separating the compounds from the culture broth.
Abstract: The freezing of foodstuffs and other biological materials such blood products as sperm, ova, embryos and other tissues may be facilitated by applying thereto a non-toxic microorganism having an INA.sup.+ phenotype or a biogenic ice nucleating agent or a functionally equivalent protein.
Abstract: Intensely crimson colonies are obtained from Streptomyces coelicolor DSM 3030 by total digestion of the total DNA, cloning into a suitable vector, and transformation of Streptomyces lividans. Re-isolation of the plasmid DNA and cutting with BamHI results in fragments about 3.4 to 9 kb in length, on which is located the gene which determines production of the coloring agent. This gene is suitable as marker, in particular as inactivation marker, in Streptomycetes.
Type:
Grant
Filed:
August 11, 1987
Date of Patent:
October 23, 1990
Assignee:
Hoechst Aktiengesellschaft
Inventors:
Gunter Muth, Wolfgang Wohlleben, Alfred Puhler, Gerhard Wohner, Rudiger Marquardt
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: An antibiotic complex, containing three major components, has been isolated from fermentations of a new strain of the microorganism Streptomyces hirautus. The major components are new, neutral, macrolide antibiotic compounds, which are useful as antibacterial agents against certain gram-positive bacteria.
Type:
Grant
Filed:
March 10, 1989
Date of Patent:
September 11, 1990
Assignee:
Pfizer Inc.
Inventors:
Walter P. Cullen, James R. Hauske, Hiroshi Maeda, Junsuke Tone
Abstract: This invention relates to a process for preparing an antibiotic D788-7 wherein, after culturing carborubicin-producing bacteria, the obtained culture liquid is extracted in acidic conditions while stirring to be absorbed to synthetic resin, followed by desorption from the resin and elution with acetone and the resulting acetone solution containing carborubicin is converted into an antibiotic D788-7 by photo radiation, for obtaining D788-7 in the purified form from the reaction solution. The production yield for D788-7 is extremely high and its use as an antitumor agent can be made possible.
Abstract: A plasmid transformation system for Rhodococcus was developed using an Escherichia coli-Rhodococcus shuttle plasmid. Rhodococcus sp. H13-A contains three cryptic indigenous plasmids, designated pMVS100, pMVS200 and pMVS300, of 75, 19.5 and 13.4 kilobases (Kb), respectively. A 3.8 Kb restriction fragment of pMVS300 was cloned into pIJ30, a 6.3 Kb pBR322 derivative, containing the E. coli origin of replication (ori) and ampicillin resistance determinant (bla) as well as a Streptomyces gene for thiostrepton resistance, tsr. The resulting 10.1 Kb recombinant plasmid, designated pMVS301, was isolated from E. coli DH1 (pMVS301) and transformed into Rhodococcus sp. AS-50, a derivative of strain H13-A, by polyethylene glycol-assisted transformation of Rhodococcus protoplasts and selection for thiostrepton-resistant transformants. This strain was deposited with the ATCC on Feb. 1, 1988 and assigned ATCC 53719.The plasmid contains the Rhodococcus origin of replication.
Type:
Grant
Filed:
February 1, 1988
Date of Patent:
August 28, 1990
Assignee:
University of Georgia Research Foundation, Inc.
Abstract: The carG gene of Streptomyces thermotolerans has been isolated and used to construct recombinant DNA expression vectors. The carG gene encodes the activities required for the biosynthesis of the 16-member cyclic lactone of carbomycin. The carG gene can be used not only to construct recombinant cells with an increased ability to produce carbomycin but also to construct recombinant cells with the ability to produce novel antibiotic compounds.
Abstract: The invention relates to compounds of antitumor activity of the formula: ##STR1## ps in which R.sup.1 is hydrogen, lower allkyl, halo(lower)alkyl or aryl,R.sup.2 is hydrogen, hydroxy or protected hydroxy,R.sup.3 is hydrogen,R.sup.4 is aminocarboxy(lower)alkyl, protected amino(lower)alkyl or protected aminocarboxy(lower)alkyl, andR.sup.5 is hydrogen or lower alkyl, or its pharmaceutical acceptable salt.
Abstract: UCN-01 having an anti-tumor activity and an anti-bacterial activity is produced by culturing a microorganism belonging to the genus Streptomyces.
Abstract: The invention relates to a method for microbiologically resolving racemic 2,3-o-substituted glycerol esters to obtain optically activated 2,3-o-substituted glycerol with remaining esters also being optically active.
Type:
Grant
Filed:
September 9, 1985
Date of Patent:
June 5, 1990
Assignee:
The Wisconsin Alumni Research Foundation
Abstract: An animal growth promoter, efomycin G, is obtained by culturing Streptomycetes strain BS 1261. Efomycin G has the following properties:(a) The empirical formula: C.sub.53 H.sub.86 O.sub.18(b) The mass spectrum (fast atom bombardment) Molecular weight+Na.sup.+ : 1033(c) The .sup.1 H-nuclear magnetic resonance spectrum, stated in parts per million, shown in FIG. 1.(d) The .sup.13 C-nuclear magnetic resonance spectrum, stated in parts per million shown in FIG. 2, with chemical shifts of the CC-NMR signals as follows:______________________________________ 170.0 77.9 65.9 32.9 7.0 145.4 73.4 48.5 19.4 144.7 71.2 43.6 19.1 131.9 70.6 41.9 16.8 121.1 70.1 41.1 16.7 99.6 69.9 38.8 15.1 99.5 66.9 38.5 13.4 93.6 66.5 36.2 9.0 93.3 66.4 33.0 8.9 ______________________________________ (ppm values are relative to tetramethylsilane at 0 ppm)(e) A UV absorption maximum at 251-254 nm in methanolic solution(f) The structure according to FIG. 3.
Type:
Grant
Filed:
March 6, 1987
Date of Patent:
May 22, 1990
Assignee:
Bayer Aktiengesellschaft
Inventors:
Klaus Frobel, Hartwig Muller, Erwin Bischoff, Olga Salcher, Anno de Jong, Friedrich Berschauer, Martin Scheer
Abstract: The antibiotic of the formula: ##STR1## wherein R is ##STR2## The antibiotic is useful for the treatment of swine dysentery and for promoting growth and/or increasing the efficiency of food utilization in poultry, swine and ruminants.
Type:
Grant
Filed:
December 16, 1987
Date of Patent:
April 24, 1990
Assignee:
Pfizer Inc.
Inventors:
Kelvin S. Holdom, John C. Ruddock, Junsuke Tone, Hiroshi Maeda, Martin R. Jefson
Abstract: An acidic polycyclic ether antibiotic, having structure established by X-ray crystallography, is formed by fermentation of a novel microorganism, Streptomyces sp. ATCC 53862. This novel antibiotic is useful as an anticoccidial in chickens, in the prevention or treatment of swine dysentery, and as a growth promotant in cattle and swine.
Type:
Grant
Filed:
February 27, 1989
Date of Patent:
April 24, 1990
Assignee:
Pfizer Inc.
Inventors:
Walter P. Cullen, James R. Hauske, Gloria J. Kostek, Hiroshi Maeda, Junsuke Tone
Abstract: A tandem arrangement of two promoters which are each active in Streptomyces is provided. The tandem arrangement provides a considerable increase in protein expression.
Abstract: S. ghanaensis DSM 2932 is resistant to gentamicin at up to 20 .mu.g/ml. Total digestion of the genomic DNA with BglII, incorporation of the restriction fragments into a suitable plasmid, and selection using gentamicin results in gentamicin-resistant clones which contain a 7 kb fragment with the gentamicin-resistance gene. The plasmid pPH1JI likewise contains a gentamicin-resistance gene located on a 2.3 kb HindIII-BamHI fragment. These genes are suitable as markers, in particular for Streptomycetes vectors.
Type:
Grant
Filed:
April 30, 1987
Date of Patent:
April 17, 1990
Assignee:
Hoechst Aktiengesellschaft
Inventors:
Wolfgang Wohlleben, Gunter Muth, Alfred Puhler
Abstract: This invention deals with the solubilization of coal using species of Streptomyces. Also disclosed is an extracellular component from a species of Streptomyces, said component being able to solubilize coal.
Type:
Grant
Filed:
January 21, 1988
Date of Patent:
April 3, 1990
Assignee:
The United States of America as represented by the United States Department of Energy
Abstract: The carB gene is a novel carbomycin resistance-conferring gene isolated from Streptomyces thermotolerans and used to construct a number of cloning vectors for use in Streptomyces and related organisms. One such coloning vector, plasmid pOJ159, can be obtained in S. griseofuscus C581 under the accession number NRRL 18090. S. lividans and S. griseofuscus are the preferred hosts when the carB gene is used to select carbomycin-resistant Streptomyces transformants.
Abstract: An antibiotic has been isolated from fermentation of a new Streptomyces culture. The new ionophore is active as an antibacterial and anticoccidial agent.
Type:
Grant
Filed:
February 29, 1988
Date of Patent:
March 13, 1990
Assignee:
Pfizer Inc.
Inventors:
Walter P. Cullen, John R. Oscarson, Junsuke Tone, Hiroshi Maeda
Abstract: The carA gene is a novel carbomycin resistance-conferring gene isolated from Streptomyces thermotolerans and used to construct a number of cloning vectors for use in Streptomyces and related organisms. One such cloning vector, plasmid pOJ158, can be obtained in S. griseofuscus C581 under the accession number NRRL 18089. S. lividans and S. griseofuscus are the preferred hosts when the carA gene is used to select carbomycin-resistant Streptomyces transformants.
Abstract: A novel gene conferring resistance to spiramycin in Streptomyces griseofuscus was cloned from a genomic library of Streptomyces ambofaciens DNA. An eighteen kb fragment of S. ambofaciens DNA surrounding the spiramycin resistance gene was isolated from this library on a plasmid cosmid designated pKC514. The novel spiramycin-resistance gene can be isolated on an .about.3.4 kb Sau3AI fragment by subcloning restriction fragments obtained from the pKC514 insert DNA. This Sau3AI fragment contains all of the information required for the expression of the spiramycin resistant phenotype in Streptomyces. Vectors and transformants containing the novel spiramycin resistance gene are provided.
Abstract: New antibiotic A80915 and its dehydrochlorination derivatives are useful antibacterial agents. Methods of making antibiotic A80915 by culture of Streptomyces aculeolatus, NRRL 18422, and compositions containing an A80915 antibiotic also are provided.
Type:
Grant
Filed:
December 27, 1988
Date of Patent:
February 27, 1990
Assignee:
Eli Lilly and Company
Inventors:
David S. Fukuda, Jon S. Mynderse, Raymond C. Yao
Abstract: Compounds as described having the partial formula ##STR1## These compounds may have a 5-OH or --OMe group amd at the 25- position an isopropylene group substituted by methyl, ethyl or isopropyl.The compounds may be used in agriculture or medicine as antiparasitics, and may be prepared by culturing certain Streptomyces strains, in particular Streptomyces thermoarchaensis NCIB 12015.
Type:
Grant
Filed:
March 25, 1987
Date of Patent:
February 6, 1990
Assignee:
American Cyanamid Company
Inventors:
John B. Ward, Hazel M. Noble, Neil Porter, Richard A. Fletton, David Noble
Abstract: 4'-Deoxy-13(S)-dihydro-4'-iododoxorubicin having the formula (II): ##STR1## and pharmaceutically acceptable salts thereof are anti-tumor agents.
Type:
Grant
Filed:
January 19, 1988
Date of Patent:
January 23, 1990
Assignee:
Farmitalia Carlo Erba S.p.A.
Inventors:
Giuseppe Cassinelli, Teresa Bordoni, Sergio Merli, Giovanni Rivola
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: 2-amino-2-deoxy-D-mannitol is produced from a microorganism strain of the genus Streptomyces or a mutant strain thereof in improved yields and purity.
Abstract: A method for introducing hydroxyl groups into vitamin D compounds at 1.alpha.- and/or 25-positions by use of a solution containing the mycelium of Actinomycetales being capable of hydroxylating vitamin D compound or the enzyme produced from the mycelium, is disclosed.
Abstract: A process for the preparation of a pharmaceutically active compound in a stereospecific form of the formula ##STR1## or a pharmaceutically acceptable salt or ester thereof, like an alkali metal salt or an alkaline earth metal salt or a pivaloyl ester, wherein R.sub.1 represents an optionally substituted aryl group such as a phenyl or naphthyl group optionally included in a heterocyclic ring system, which is optionally substituted, or represents a heteroaromatic ring system containing in addition to carbon atoms one or more atoms selected from nitrogen, sulphur and oxygen, this ring system being optionally substituted, which comprises subjecting a compound of the formula ##STR2## wherein R.sub.
Type:
Grant
Filed:
January 6, 1987
Date of Patent:
December 12, 1989
Assignees:
Gist-Brocades N.V., Shell Internationale Research Mattschappij B.V.
Inventors:
Mauro A. Bertola, Arthur F. Marx, Hein S. Koger, Wilhelmus J. Quax, Cornelis J. Van der Laken, Gareth T. Phillips, Brian W. Robertson, Peter D. Watts