Hydroxylating Patents (Class 435/58)
  • Patent number: 8852885
    Abstract: Methods and compositions for the production of oil, fuels, oleochemicals, and other compounds in recombinant microorganisms are provided, including oil-bearing microorganisms and methods of low cost cultivation of such microorganisms. Microalgal cells containing exogenous genes encoding, for example, a lipase, a sucrose transporter, a sucrose invertase, a fructokinase, a polysaccharide-degrading enzyme, a keto acyl-ACP synthase enzyme, a fatty acyl-ACP thioesterase, a fatty acyl-CoA/aldehyde reductase, a fatty acyl-CoA reductase, a fatty aldehyde reductase, a fatty acid hydroxylase, a desaturase enzyme, a fatty aldehyde decarbonylase, and/or an acyl carrier protein are useful in manufacturing transportation fuels such as renewable diesel, biodiesel, and renewable jet fuel, as well as oleochemicals such as functional fluids, surfactants, soaps and lubricants.
    Type: Grant
    Filed: July 12, 2012
    Date of Patent: October 7, 2014
    Assignee: Solazyme, Inc.
    Inventors: Scott Franklin, Aravind Somanchi, Janice Wee, George Rudenko, Jeffrey L. Moseley, Walt Rakitsky, Xinhua Zhao, Riyaz Bhat
  • Publication number: 20130040341
    Abstract: The invention relates to novel 7?-hydroxysteroid dehydrogenases which are obtainable from bacteria of the genus Collinsella, especially of the strain Collinsella aerofaciens, to the sequences encoding said enzymes, to methods for producing said enzymes and to their use in the enzymatic conversion of cholic acid compounds, and especially in the production of ursodeoxycholic acid (UDCS). The invention also relates to novel methods for the synthesis UDCS.
    Type: Application
    Filed: November 30, 2010
    Publication date: February 14, 2013
    Applicant: PhamaZell GmbH
    Inventors: Luo Liu, Rolf Schmid, Arno Aigner
  • Publication number: 20120231495
    Abstract: This invention relates to the production of 7-dehydrocholesterol, 25-hydroxy-7-dehydrocholesterol, and 25-hydroxy ergosterol in yeast such as Saccharomyces cerevisiae. It also related to various enzymes catalyzing the reduction of the double bond at position 24 of lanosterol, dimethyl zymosterol, methyl zymosterol, zymosterol, cholesta-7, 24-dienol, or cholesta-5,7,24-trienol; or the hydroxylation at position 25 of ergosterol, 7-dehydrocholesterol, cholesta-8-enol, and cholesta-7-enol. It also relates to various nucleic acids encoding cholesterol C25-hydroxylases and sterol ?24-reductases and their use to produce and hydroxylate 7-dehydrocholesterol or ergosterol. It also relates to the yeast strains so produced, and methods of making these sterols comprising the steps of cultivation a transformed yeast cell, and harvesting the resulting sterol(s).
    Type: Application
    Filed: November 24, 2010
    Publication date: September 13, 2012
    Inventors: Hans-Peter Hohmann, Martin Lehmann, Muriel Merkamm, Denis Pompon
  • Patent number: 8198041
    Abstract: A method of producing ?1,4-Tibolone (C21H26O2), 10?-Hydroxy-?4-tibolone (C21H28O3). 11?,15?-Dihydroxytibolone (C21H28O4) and 11?,15?-Dihydroxy-?5-tibolone (C21H28O4) by contacting tibolone and 3?,6?-Dihydroxytibolone (C21H32O3) by contacting 3?-hydroxytibolone with Cunninghamella elegans (ATCC 10028b) is reported.
    Type: Grant
    Filed: January 27, 2011
    Date of Patent: June 12, 2012
    Inventors: Attaur Rahman, Muhammed Iqbal Choudhary, Syed Adnan Ali Shah, Shamsun Nahar Khan
  • Patent number: 8148556
    Abstract: A new method of producing metabolites of tibolone comprising fermenting tibolone with Rhizopus stolonifer (ATCC 12938) resulting in the formation of ?4-Tibolone (C21H28O2), 6?-Hydroxytibolone, and 15?-Hydroxytibolone (C21H28O3) is reported.
    Type: Grant
    Filed: January 27, 2011
    Date of Patent: April 3, 2012
    Inventors: Attaur Rahman, Muhammed Iqbal Choudhary, Syed Adnan Ali Shah, Shamsun Nahar Khan
  • Patent number: 7977065
    Abstract: The present invention relates to genetically modified yeast strains autonomously producing, from a simple carbon source, steroids. The invention also relates to a method for producing steroids from such yeast strains.
    Type: Grant
    Filed: January 7, 2010
    Date of Patent: July 12, 2011
    Assignee: Aventis Pharma S.A.
    Inventors: Roberto Spagnoli, Tilman Achstetter, Gilles Cauet, Eric Degryse, Bruno Dumas, Denis Pompon, Jacques Winter
  • Publication number: 20110124044
    Abstract: A method of producing ?1,4-Tibolone (C21H26O2), 10?-Hydroxy-?4-tibolone (C21H28O3). 11?,15?-Dihydroxytibolone (C21H28O4) and 11?,15?-Dihydroxy-?5-tibolone (C21H28O4) by contacting tibolone and 3?,6?-Dihydroxytibolone (C21H32O3) by contacting 3?-hydroxytibolone with Cunninghamella elegans (ATCC 10028b) is reported.
    Type: Application
    Filed: January 27, 2011
    Publication date: May 26, 2011
    Applicant: INTERNATIONAL CENTER FOR CHEMICAL SCIENCES
    Inventors: Attaur Rahman, Mohammed Iqbal Choudhary, Syed Adnan Ali Shah, Shamsun Nahar Khan
  • Publication number: 20110124043
    Abstract: Method of producing ?5-Tibolone (C21H28O2), 6?-Hydroxy-?4-tibolone (C21H28O3), 6?-Hydroxy-?4-tibolone (C21H28O3), 15?-Hydroxy-?4-tibolone (C21H28O3), 6?-Hydroxy-?1,4-tibolone (C21H28O3) and 6?-Methoxy-?4-tibolone (C22H30O3) contacting tibolone with Gibberella fujikuroi (ATCC 10704) is reported.
    Type: Application
    Filed: January 27, 2011
    Publication date: May 26, 2011
    Applicant: INTERNATIONAL CENTER FOR CHEMICAL SCIENCES
    Inventors: Attaur Rahman, Mohammad Iqbal Choudhary, Syed Adnan Ali Shah, Shamsun Nahar Khan
  • Publication number: 20110118228
    Abstract: Provided herein are steroidal compounds that are androsta-5,7-dienes or a pregna-5,7-dienes and ultraviolet B (UVB) conversion products thereof which includes pharmaceutical compositions of the steroidal compounds as shown in Tables 1 and 2. Also provided is a method for producing hydroxylated metabolites of cholecalciferol or ergocalciferol via the P450scc (CYP11A1) or CYP27B1 enzyme systems where the hydroxylase has an activity to hydroxylate position C20 of a secosteroid or its 5,7-dieneal precursor and the hydroxylated metabolites so produced. In addition, a method for inhibiting proliferation of either a normally or abnormally proliferating cell by contacting the cell with any of the compounds described herein. A related method is provided of treating a condition associated with the proliferating cell such as a cancer, a skin disorder, a defect in cell differentiation, cosmetic, prophylaxsis, or healthy cell maintenance.
    Type: Application
    Filed: August 30, 2010
    Publication date: May 19, 2011
    Inventors: Andrzej Slominski, Wei Li, Blazej Zbytek, Robert C. Tuckey, Jordan K. Zjawiony, Minh Ngoc Nguyen, Zorica Janjetovic, Michal A. Zmijewski, Trevor W. Sweatman, Duane D. Miller, Jianjun Chen, Arnold E. Postlethwaite
  • Patent number: 7829027
    Abstract: A sample carrier with a sample receiver for the sample liquid and with preferably several sample chambers which are connected thereto is proposed. In order to avoid refilling with sample liquid when it evaporates or is otherwise lost or used up, there is additionally a reservoir for sample liquid which is covered in the same way as the sample chambers and which has a connecting channel to the environment which can be closed by the sample liquid.
    Type: Grant
    Filed: November 22, 2004
    Date of Patent: November 9, 2010
    Assignee: Boehringer Ingelheim microParts GmbH
    Inventors: Dirk Osterloh, Ralf-Peter Peters
  • Patent number: 7670829
    Abstract: The present invention relates to genetically modified yeast strains autonomously producing, from a simple carbon source, steroids. The invention also relates to a method for producing steroids from such yeast strains.
    Type: Grant
    Filed: January 29, 2002
    Date of Patent: March 2, 2010
    Assignee: Aventis Pharma S.A.
    Inventors: Roberto Spagnoli, Tilman Achstetter, Gilles Cauet, Eric Degryse, Bruno Dumas, Denis Pompon, Jacques Winter
  • Patent number: 7588888
    Abstract: Regulation of expression of programmed cell death, including senescence, in plants is achieved by integration of a gene or gene fragment encoding senescence-induced deoxyhypusine synthase, senescence-induced elF-5A or both into the plant genome in antisense orientation. Plant genes encoding senescence-induced deoxyhypusine synthase and senescence-induced elF-5A are identified and the nucleotide sequences of each, alone and in combination are used to modify senescence in transgenic plants.
    Type: Grant
    Filed: May 27, 2004
    Date of Patent: September 15, 2009
    Assignee: Senesco Technologies, Inc.
    Inventors: John E. Thompson, Tzann-Wei Wang, Dongen Lily Lu
  • Patent number: 7575892
    Abstract: Soyasapogenol B is biosynthesized via two steps of hydroxylation reaction of its precursor ?-amyrin. However, the gene of the hydroxylase concerned in this reaction has not been revealed. Therefore, it was impossible to apply a genetic engineering technique on the hydroxylase. The present inventors reveals that a sequence which corresponds to a soybean-derived cytochrome P-450 gene CYP93E1 encodes an enzyme protein that carries out hydroxylation of the 24-position of an oleanane type triterpene, and also provides a method for applying said gene making use of a genetic engineering technique.
    Type: Grant
    Filed: February 25, 2005
    Date of Patent: August 18, 2009
    Assignee: Meiji Seika Kaisha, Ltd.
    Inventors: Hiroaki Hayashi, Kenichiro Inoue, Masateru Hoshino, Masaaki Shibuya, Yutaka Ebizuka
  • Publication number: 20090137542
    Abstract: Sixteen new and one known metabolites were obtained by incubation of tibolone and hydroxytibolones with various fungi. Their structures were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS techniques. The relative stereochemistry was deduced by 2D NOESY experiment. These metabolites have shown promising inhibitory activities against ?-glucosidase enzyme. Seven metabolites exhibited potent inhibitory activity against the ?-glucosidase enzyme and were thus found useful in the treatment of diabetes mellitus and other diseases related to the activity of ?-glucosidase enzyme.
    Type: Application
    Filed: November 23, 2007
    Publication date: May 28, 2009
    Applicant: International Center for Chemical Sciences
    Inventors: Attaur Rahman, Muhammed Iqbal Choudhary, Syed Adnan Ali Shah, Shamsun Nahar Khan
  • Publication number: 20090117613
    Abstract: A method of selective biooxidation to non activated carbon-hydrogen bonds of substances using a Geobacillus kaustophilus ‘Old Yellow Enzyme’ is provided”. It is shown that OYEs can be used to facilitate the biooxydation of substances, such as testosterone. It is also shown that OYE can introduce double bonds to form alpha, betaalpha, beta desaturated ketones. Furthermore, it is also shown that the use of OYEs allows for the production of oxidized substances in one step reactions, which are otherwise not accessible or only accessible after complex and inefficient multi-step reactions. In addition, the OYE used shows high stability (e.g. at high temperature, or in long lasting bioconversions). An exemplary embodiment is provided showing the use of an OYE to convert testosterone to 6?-hydroxytestosterone.
    Type: Application
    Filed: May 15, 2008
    Publication date: May 7, 2009
    Inventors: Anton Glieder, Matthias Schittmayer, Spiros Kambourakis, Simone Zach
  • Publication number: 20090117612
    Abstract: A method for a chemoselective and regioselective enzyme mediated oxidation of carbon-hydrogen bonds of substrates using a Geobacillus kaustophilus ‘Old Yellow Enzyme’ is provided. It is shown that OYEs can be used to facilitate the bioxidation of substrates, such as testosterone. It is also shown that the use of OYEs allows for the production of oxidized substrates in one step reactions, which are otherwise not accessible or only accessible after complex and inefficient multi-step reactions. In addition, the OYE used shows high stability at high temperature. An exemplary embodiment is provided showing the use of an OYE to convert testosterone to 6?-hydroxytestosterone.
    Type: Application
    Filed: May 2, 2008
    Publication date: May 7, 2009
    Inventors: Anton Glieder, Mattias Schittmayer
  • Patent number: 7514236
    Abstract: The invention relates to an isolated polynucleotide sequence comprising a nucleic acid sequence encoding the amino acid sequence of KshA protein or of KshB protein, encoded by nucleotides 499-1695 of SEQ ID NO:1 or by nucleotides 387-1427 of SEQ ID NO:2, respectively, and functional homologues thereof. The polynucleotides of the invention can be used to construct genetically modified microorganisms blocked in 3-ketosteroid 9?-hydroxylase activity, which are useful in the microbial degradation of steroids to accumulate certain steroid products.
    Type: Grant
    Filed: January 18, 2007
    Date of Patent: April 7, 2009
    Assignee: N.V. Organon
    Inventors: Robert Van Der Geize, Peter Van Der Meijden, Gerda Hessels, Lubbert Dijkhuizen
  • Patent number: 7405057
    Abstract: The invention features isolated cytochrome P450 polypeptides and nucleic acid molecules, as well as expression vectors and transgenic plants containing these molecules. In addition, the invention features uses of such molecules in methods of increasing the level of resistance against a disease caused by a plant pathogen in a transgenic plant, in methods for producing altered compounds, for example, hydroxylated compounds, and in methods of producing isoprenoid compounds.
    Type: Grant
    Filed: March 8, 2002
    Date of Patent: July 29, 2008
    Assignee: Board of Trustees of the University of Kentucky
    Inventors: Joseph Chappell, Lyle F. Ralston
  • Patent number: 7033779
    Abstract: The invention concerns a novel method for producing hydroxylated and/or acetylated steroid comprising steps which consist in: culturing yeasts on a medium comprising at least a precursor of such hydroxylated and/or acetylated steroids; then isolating the hydroxylated and/or acetylated steroids from the medium after bioconversion. Said method is characterized in that said yeasts are yeasts transformed so as to express the product of Cyp7b gene. The invention also concerns the modified yeast strains.
    Type: Grant
    Filed: October 4, 2000
    Date of Patent: April 25, 2006
    Assignee: Transgene S.A.
    Inventors: Gilles Cauet, Eric Degryse, Pedro Vico, Richard Lathe
  • Publication number: 20040265827
    Abstract: Reagents that regulate human steroid 5-alpha reductase and reagents which bind to human steroid 5-alpha reductase gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, cancer, particularly prostate cancer or urological disorders.
    Type: Application
    Filed: August 5, 2004
    Publication date: December 30, 2004
    Inventor: Zhimin Zhu
  • Patent number: 6828120
    Abstract: The present invention is a novel process for the transformation of 17&agr;-hydroxy-6&agr;-methylpregn-4-ene-3,20-dione 17-acetate (I) to 11&bgr;,17&agr;,21-trihydroxy-6&agr;-methylpregna-1,4-diene-3,20-dione 21-acetate (VI)
    Type: Grant
    Filed: June 14, 2002
    Date of Patent: December 7, 2004
    Assignee: Pharmacia and Upjohn Company
    Inventors: Bruce Allen Pearlman, Michael J. White, Ivan G. Gilbert
  • Publication number: 20040171853
    Abstract: The invention relates to a fungal process to prepare 5-androsten-3&bgr;,7&agr;,15&agr;-triol-17-one and related analogues.
    Type: Application
    Filed: February 5, 2004
    Publication date: September 2, 2004
    Inventors: Michael Jon White, Ivan Gale Gilbert
  • Patent number: 6632633
    Abstract: An expression cassette, operable in a recombinant host, comprising a heterologous DNA coding sequence encoding a protein, which is functional, alone or in cooperation with one or more additional proteins of catalyzing an oxidation step in the biological pathway, for conversion of cholesterol into hydrocortisone, which step is selected from the group consisting of: the conversion of cholesterol to pregnenolone; the conversion of pregnenolone to progesterone; the conversion of progesterone to 17&agr;-hydroxyprogesterone; the conversion of 17&agr;-hydroxyprogesterone to cortexolone; the conversion of cortexolone to hydrocortisone, and the corresponding control sequences effective in that host.
    Type: Grant
    Filed: June 17, 1998
    Date of Patent: October 14, 2003
    Assignee: Aventis Pharma, S.A.
    Inventors: Herman Slijkhuis, Eric Bastiaan Smaal, Gerardus Cornelis Maria Selten
  • Patent number: 6605591
    Abstract: A method of treating an individual to increase the individual's bone mineral density (BMD) is disclosed. The method includes co-administering a calcitonin-like agent and a DHEA-like agent. Also disclosed are methods for potentiating the effect of treatment with a calcitonin-like agent on BMD and for increasing BMD in an individual being treated with DHEA, e.g., for treatment of systemic lupus erythematosus (SLE).
    Type: Grant
    Filed: November 10, 2000
    Date of Patent: August 12, 2003
    Assignee: Genelabs Technologies, Inc.
    Inventor: Kenneth E. Schwartz
  • Patent number: 6579693
    Abstract: Yeast strains expressing human genes coding regulating cytochrome P450 expression, a method for making same and applications thereof are described.
    Type: Grant
    Filed: February 2, 2000
    Date of Patent: June 17, 2003
    Assignees: Aventis Pharma S.A., Centre National de la Recherche Scientifique
    Inventors: Aouatef Bellamine, Frédéric Delorme, Alain Perret, Denis Pompon
  • Publication number: 20030082791
    Abstract: Strains of bacteria characterized by exhibiting: (a) a 7&agr;-dehydroxylase activity of less than 50%, and (b) a bile acid deconjugation activity of less than 50%, and descendants, mutants and derivatives thereof preserving activities (a) and (b); and a pharmaceutical composition using one or more of such strains and use of same for preventing and treating diseases associated with or caused by an altered metabolism of bile acids.
    Type: Application
    Filed: June 18, 2002
    Publication date: May 1, 2003
    Inventor: Claudio De Simone
  • Publication number: 20020031798
    Abstract: The present invention relates to a polypeptide having 25-hydroxyvitamin D3-1&agr;-hydroxylase activity, being useful for the prevention, diagnosis and therapeutic treatment of adult diseases such as osteoporosis induced by the decrease of active type vitamin D3 and catalyzing the final stage of vitamin D3 activation; and the gene encoding the polypeptide.
    Type: Application
    Filed: June 12, 2001
    Publication date: March 14, 2002
    Inventors: Hideharu Anazawa, Hiroko Shimada, Seiji Sugimoto, Tatsuo Suda, Toshimasa Shinki, Takao Saruta, Yuzuru Ishimura, Matsuhiko Hayashi, Shu Wakino, Toshiaki Monkawa, Tadashi Yoshida, Hiromichi Suzuki
  • Patent number: 6156946
    Abstract: The present invention is a process for transforming aromatic organic compounds and resource materials. The process includes the steps of contacting an organic material selected from the group consisting of single and/or multi-ring aromatic compounds and alkylaromatic compounds, and their heteroatom-containing analogues, crude oil, petroleum, petrochemical streams, coals, shales, coal liquids, shale oils, heavy oils and bitumens with a microorganism or enzymes in order to hydroxylate the organic material, followed by contacting the hydroxylated organic resource material so as to cause hydrogenation and/or hydrogenolysis on the material.
    Type: Grant
    Filed: October 8, 1999
    Date of Patent: December 5, 2000
    Assignee: Exxon Research and Engineering Company
    Inventors: Catherine L. Coyle, Michael Siskin, David T. Ferrughelli, Michael S. P. Logan, Gerben Zylstra
  • Patent number: 6043050
    Abstract: A biological process for producing steroids hydroxylated at the 25-position thereof comprises adding steroids (excluding cholesterol) to the cells or culture liquid of a microorganism of the genus Amycolata or Sphingomonas capable of hydroxylating the steroids at the 25-position thereof to convert a hydrogen atom bonded to a carbon atom at the 25-position of each steroid into hydroxyl group. By this process, steroids(other than cholesterol) can be biologically hydroxylated at the 25-position by using microorganisms other than those of the genus Streptomyces.
    Type: Grant
    Filed: December 23, 1998
    Date of Patent: March 28, 2000
    Assignees: Mercian Corporation, Chugai Seiyaku Kabushiki Kaisha
    Inventors: Koji Takeda, Tadashi Terasawa, Kazuyuki Dobashi, Takeo Yoshioka
  • Patent number: 5989855
    Abstract: A microorganism having a capability of introducing a 7.beta.-hydroxyl group into a 7-unsubstituted bile acid, and a process for preparing a bile acid having a 7.beta.-hydroxyl group characterized by bringing the above microorganism into contact with a 7-unsubstituted bile acid to convert the acid to a bile acid having a 7.beta.-hydroxyl group. The process permits ursodeoxycholic acid useful as a cholagogue and intermediates therefor to be efficiently prepared.
    Type: Grant
    Filed: September 29, 1998
    Date of Patent: November 23, 1999
    Assignee: Tokyo Tanabe Company Limited
    Inventors: Akio Okamura, Hiroyuki Matsui
  • Patent number: 5384419
    Abstract: An improved process for the preparation of 20-keto-21(S)-hydroxy steroids of the Formula ##STR1## wherein R.sub.1 is alkyl of 1 to 3 carbon atoms, R.sub.2 is alkyl of 1 to 12 carbon atoms, and R.sub.3 is alkyl of 1 to 4 carbon atoms and novel intermediates therefrom.
    Type: Grant
    Filed: June 2, 1993
    Date of Patent: January 24, 1995
    Assignee: Roussel-Uclaf
    Inventors: Jean Buendia, Jean-Yves Godard, Philippe Mackiewicz, Christian Richard
  • Patent number: 5378611
    Abstract: The invention provides a novel process for the production of 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione which comprises culturing a microorganism belonging to the genus Myrothecium and capable of hydrolyzing 4-androstene-3,17-dione to produce 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione in a medium supplemented with 4-androstene-3,17-dione, and isolating 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione from the cultured medium. According to the process of the present invention, 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione and 14.alpha.-hydroxy-4-androstene-3,6,17-trione can be produced with a high yield in a simple manner.
    Type: Grant
    Filed: November 19, 1993
    Date of Patent: January 3, 1995
    Assignee: Nippon Kayaku Kabushiki Kaisha
    Inventors: Hideki Yoshioka, Hajime Asada, Shinji Fujita
  • Patent number: 5298398
    Abstract: 9.alpha.-hydroxy-17-keto steroids are prepared by fermenting steroids having a C-17-side chain of 5-10 carbon atoms inclusive, with the novel Mycobacterium species CBS 482.86. Starting from various substrates containing a 5-10 C carbon chain on C-17, 9.alpha.-hydroxyandrost-4-ene-3,17-dione, 7.alpha.,9.alpha.,12.alpha.-trihydroxyandrost-4-ene-3,17-dione or 9.alpha.-hydroxyandrost-4,11-diene-3,17-dione is obtained in high yield. The resulting compounds are useful intermediates in the synthesis of therapeutically important steroids, particularly corticosteroids.
    Type: Grant
    Filed: August 6, 1992
    Date of Patent: March 29, 1994
    Assignee: Gist-Brocades NV
    Inventors: Harmen Slijkhuis, Arthur F. Marx
  • Patent number: 5183749
    Abstract: The present invention relates to a one-step microbial process for the preparation of 13.beta.-hydroxy- or 14,15-epoxy-milbemycins of the following formulae I and II ##STR1## in which R.sub.1 and R.sub.1 ' represent methyl, ethyl, isopropyl or sec.-butyl or represent the group ##STR2## in which X represents methyl, ethyl or isopropyl, and A and A' represent the group ##STR3## in which R.sub.2 represents hydrogen, --C(O)-CH.sub.2 O-C(O)-CH.sub.2 CH.sub.2 -COOH or --C(O)-CH.sub.2 CH.sub.2 -COOH, or mixtures of compounds of the formulae I and II, which process comprises bringing a milbemycin of the formula III ##STR4## dissolved in a liquid phase, in which R.sub.3 represents R.sub.1 or R.sub.1 ' and R.sub.4 represents A or A', and R.sub.1, R.sub.1 ', A and A' have the meanings given for formulae I and II, into contact with a microorganism that is capable of 13.beta.-hydroxylation or 14,15-epoxidation or of both reactions, or into contact with active constituents thereof.
    Type: Grant
    Filed: March 20, 1990
    Date of Patent: February 2, 1993
    Assignee: Sankyo Company, Ltd.
    Inventors: Gerado Ramos, Oreste Ghisalba, Hans-Peter Schar, Bruno Frei, Peter Maienfisch, Anthony C. O'Sullivan
  • Patent number: 5164302
    Abstract: Novel 7.beta.-hydroxy-4-pregnene-3,20-dione derivatives are disclosed.The group of these compounds has possibility of being utilized as an intermediate for the synthesis of progesterone derivatives having ovulation-inhibiting activity. These compounds themselves have also cell differentiation activity for M1 cells.
    Type: Grant
    Filed: November 15, 1989
    Date of Patent: November 17, 1992
    Assignee: Snow Brand Milk Products Company, Limited
    Inventors: Makoto Yoshihama, Koji Tamura, Nobuo Miyata, Masamichi Nakakoshi
  • Patent number: 4997755
    Abstract: A microbiological process is described for the preparation of 6-desmethyl-6-.beta.-hydroxymethyl and 6-desmethyl-6-.beta.-carboxylovastatin derivatives and 8-acyl analogs thereof.
    Type: Grant
    Filed: April 14, 1988
    Date of Patent: March 5, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Joanne M. Williamson, David Houck, Edward S. Inamine
  • Patent number: 4975368
    Abstract: Novel androst-4-ene-3,17-dione derivatives are disclosed. The group of these compounds has biological activities, in particular, the inhibiting activity on human placenta-derived estrogen-synthesizing enzyme. Therefore these compounds are expected to be utilized in the field of medical care, particularly as anticancer drugs.
    Type: Grant
    Filed: September 26, 1988
    Date of Patent: December 4, 1990
    Assignee: Snow Brand Milk Products Co., Ltd.
    Inventors: Makoto Yoshihama, Koji Tamura, Nobuo Miyata, Shoji Nakayama, Masamichi Nakakoshi
  • Patent number: 4963450
    Abstract: A laminated layer type electrophotographic photosensitive member has a charge generation layer and a charge transport layer on an electroconductive support, characterized in that the charge generation layer has at least one of disazo pigments represented by the formulae (1) and (2).
    Type: Grant
    Filed: January 13, 1989
    Date of Patent: October 16, 1990
    Assignee: Canon Kabushiki Kaisha
    Inventors: Hajime Miyazaki, Shintetsu Go, Akihiro Senoo, Kazushi Iuchi, Tetsuro Kanemaru
  • Patent number: 4604353
    Abstract: A one step method of producing conjugated ursodeoxycholic acids from conjugated lithocholic acids by means of microbial transformation which comprises subjecting the conjugated lithocholic acids to the action of microorganisms which belong to Mortierella and which are capable of producing conjugated ursodeoxycholic acids from conjugated lithocholic acids.
    Type: Grant
    Filed: February 24, 1984
    Date of Patent: August 5, 1986
    Assignee: Kabushiki Kaisha Yakult Honsha
    Inventors: Haruji Sawada, Masaaki Watanuki
  • Patent number: 4579819
    Abstract: A one-step method of producing ursodeoxycholic acid by means of microbial transformation which comprises subjecting lithocholic acid to the action of a ursodeoxycholic acid producing microorganism.
    Type: Grant
    Filed: March 2, 1983
    Date of Patent: April 1, 1986
    Assignee: Kabushiki Kaisha Yakult Honsha
    Inventors: Haruji Sawada, Hisaharu Taguchi
  • Patent number: 4528271
    Abstract: Microbiological conversions of cyclodextrins are intensified by adding to the reaction mixture 0.2 to 3 moles of .alpha.-, .beta.- or .gamma.-cyclodextrin or an optical mixture thereof pro mole of the steroid substrate, before, at the beginning or during the conversion. The cyclodextrin if desired, can be removed after the reaction. In this way the reaction velocity can be increased, the reaction time is reduced, the substrate concentration in the solution, i.e. its solubility is increased or the so called product inhibition may be avoided. In certain cases of more alternatives the desired reaction can be catalyzed and in this manner the selectivity is increased.
    Type: Grant
    Filed: September 24, 1982
    Date of Patent: July 9, 1985
    Assignees: Richter Gedeon Vegyeszeti Gyar Rt., Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt.
    Inventors: Eva Udvardy Nagy nee Cserey Pechany, Istvan Bartho, Gabor Hantos, Maria Trinn, Zsuzsa Vida, Jozsef Szejtli, Agnes Stadler nee Szoke, Ilona Habon, Marta Balazs nee Czurda
  • Patent number: 4429041
    Abstract: The subject invention concerns a novel one-stage fermentation process for making the useful steroid intermediate 9-hydroxy-3-oxo-4,17(20)-pregnadiene-20-carboxylic acid (I). This process is significantly superior to the best prior art process known for making (I).
    Type: Grant
    Filed: May 11, 1981
    Date of Patent: January 31, 1984
    Assignee: The Upjohn Company
    Inventors: Merle G. Wovcha, John C. Knight, Alfred B. Garcia
  • Patent number: 4425429
    Abstract: The subject invention concerns a novel fermentation process for making the novel useful steroid intermediate 9-hydroxy-3-oxo-4,17(20)-pregnadiene-20-carboxyaldehyde (I). This compound can be used as in the synthesis of valuable corticoids.
    Type: Grant
    Filed: July 24, 1981
    Date of Patent: January 10, 1984
    Assignee: The Upjohn Company
    Inventors: John C. Knight, Merle G. Wovcha
  • Patent number: 4416985
    Abstract: A process for preparing a 3.beta.,7.beta.-dihydroxy-.DELTA..sup.5 steroid of the formula ##STR1## wherein Q is ##STR2## and R.sub.1 is hydrogen, trimethylacetyl, tert-butyldimethylsilyl, dimethyl-2-(3-methylbutyl)silyl or tribenzylsilyl,comprises fermenting a 3.beta.-hydroxy-.DELTA..sup.5 -steroid of the formula ##STR3## wherein Q is as defined above, andR.sub.2 is hydrogen or alkanoyl of 2-6 carbon atoms,with a culture of Botryodiplodia malorum to obtain the corresponding 3.beta.,7.beta.-dihydroxy-.DELTA..sup.5 -steroid; and, optionally, reacting the resultant product with trimethylacetic anhydride, tert-butyldimethylsilyl chloride, dimethyl-2-(3-methylbutyl)silyl chloride, or tribenzylsilyl chloride.
    Type: Grant
    Filed: November 3, 1981
    Date of Patent: November 22, 1983
    Assignee: Schering, Aktiengesellschaft
    Inventors: Karl Petzoldt, Rudolf Wiechert, Henry Laurent, Klaus Nickisch, Dieter Bittler
  • Patent number: 4397947
    Abstract: Valuable 9.alpha.-hydroxy steroids are prepared via microbial enzymatic oxidation (MEO) by conventional fermentation means, without the need for a .DELTA..sup.1 dehydrogenation inhibitor, utilizing novel microorganism Nocardia canicruria ATCC 31548. Also disclosed is a novel method using any .DELTA..sup.1 dehydrogenase producing organism and a novel bio-reactor technique means for preparing said steroids.
    Type: Grant
    Filed: June 12, 1981
    Date of Patent: August 9, 1983
    Assignee: G. D. Searle & Co.
    Inventors: William J. Marsheck, James Jiu, Ping T. Wang
  • Patent number: 4379842
    Abstract: The invention relates to a process for producing 1.alpha.-hydroxydehydroepiandrosterone by fermenting or reacting dehydroepiandrosterone or a derivative thereof with microorganisms of the species Penicillium oxalicum or Aspergillus terreus or mycelium or extracts therefrom obtained when the microorganisms are in a stationary phase of growth. The invention process produces steroid compounds which are pharmacologically valuable substances.
    Type: Grant
    Filed: August 24, 1981
    Date of Patent: April 12, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Akiko Fujiwara, Chikara Miyamoto, Toru Okuda
  • Patent number: 4368264
    Abstract: The present invention concerns ergostadientriols which may be recovered from either the fungus R. oligosporus or the fungus R. oryzae as well as from soybeans which have been fermented with either of these fungi. Alternatively, the sterols may be chemically synthesized. The sterols of this invention are antioxidants which may be used in anti-oxidant compositions alone or preferably with one or more isoflavone. Of particular significance is the discovery that the ergostadientriols of this invention are useful in lowering serum cholesterol levels. Accordingly, this invention in a particularly preferred embodiment discloses pharmaceutical compositions containing one or more ergostadientriol. Finally, therapeutic methods which utilize pharmaceutical compositions in accordance with this invention are disclosed.
    Type: Grant
    Filed: August 4, 1980
    Date of Patent: January 11, 1983
    Assignee: Z-L Limited Partnership
    Inventor: Fritz W. Zilliken
  • Patent number: 4336332
    Abstract: The invention relates to a process for producing 7.sub..alpha. -hydroxylated steroids by fermenting or reacting a steroid to be hydroxylated with microorganisms of the genus Botryodiplodia or enzyme extracts thereof until hydroxylation occurs. The invention process produces steroid compounds which are pharmacologically valuable substances.
    Type: Grant
    Filed: February 4, 1980
    Date of Patent: June 22, 1982
    Assignee: Hoffmann-La Roche, Inc.
    Inventors: Mitsuhiko Fujiwara, Akiko Fujiwara, Chikara Miyamoto
  • Patent number: 4303754
    Abstract: Method of producing steroids having a 7.beta.-OH substituent which comprises subjecting a steroid having a B-ring structure of the formula, ##STR1## wherein X is OH; Y is H, and when taken together X and Y is oxo (O.dbd.), to the action of a microorganism of the genus Clostridium.
    Type: Grant
    Filed: March 17, 1980
    Date of Patent: December 1, 1981
    Inventor: Ian Macdonald
  • Patent number: 4301246
    Abstract: A multi-step synthesis of chenodeoxycholic acid from 3-keto-bisnorcholenol, a compound readily obtained from the abundant plant sterol .beta.-sitosterol, is described. A key step in the synthesis is the stereoselective microbial introduction of the 7-alpha hydroxy group into 3-keto-bisnorcholenol.
    Type: Grant
    Filed: January 18, 1980
    Date of Patent: November 17, 1981
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Carl Despreaux, Thomas A. Narwid, Norberto J. Palleroni, Milan R. Uskokovic