The Hetero Ring Has Eight Or More Ring Members And Only Oxygen As Ring Hetero Atoms (e.g., Erythromycin, Spiramycin, Nystatin, Etc.) Patents (Class 435/76)
  • Patent number: 7285653
    Abstract: The present invention relates to nucleic acid coding for enzyme activities of spinosyn biosynthesis and to the relevant enzymes per se. Furthermore, the invention relates to methods for preparing spinsoyn derivatives and spinosyn precursors.
    Type: Grant
    Filed: August 17, 2000
    Date of Patent: October 23, 2007
    Assignee: Bayer Aktiengesellschaft
    Inventors: Günther Eberz, Volker Möhrle, Rita Fröde, Robert Velten, José A. Salas
  • Patent number: 7220560
    Abstract: The present invention provides a generalized oxygen-limited cultivation method for myxobacterial strains engineered to heterologously express polyketides synthase (PKS) gene clusters under various oxygen tension conditions, modulating the polyketide congener distribution.
    Type: Grant
    Filed: February 25, 2003
    Date of Patent: May 22, 2007
    Assignee: Kosan Biosciences Incorporated
    Inventors: Peter J. Licari, Bryan Julien, Scott Frykman, Hiroko Tsuruta
  • Patent number: 7208294
    Abstract: A display device and a display panel driving method, in which a matrix panel includes pixel portions each have a series circuit of a bistable element and a light emitting element, every time one scan line is specified in order in accordance with an input image signal, a driving line corresponding to at least one pixel portion to be driven to emit light on the one scan line is specified in accordance with the input image signal, a first predetermined voltage lower than a turn-off threshold voltage is applied between the one scan line and the specified driving line, and thereafter a second predetermined voltage higher than a turn-on threshold voltage is applied therebetween.
    Type: Grant
    Filed: March 12, 2004
    Date of Patent: April 24, 2007
    Assignee: Pioneer Corporation
    Inventor: Takahisa Tanabe
  • Patent number: 7198922
    Abstract: A polyketide synthase (“PKS”) of Type I is a complex multienzyme including a loading domain linked to a multiplicity of extension domains. The first extension module receives an acyl starter unit from the loading domain and each extension module adds a further ketide unit which may undergo processing (e.g. reduction). We have found that the Ksq domain possessed by some PKS's has decarboxylating activity, e.g. generating (substituted) acyl from (substituted) malonyl. The CLF domain of type II PKS's has similar activity. By inserting loading modules including such domains into PKS's not normally possessing them it is possible to control the starter units used.
    Type: Grant
    Filed: February 19, 2004
    Date of Patent: April 3, 2007
    Assignees: Biotica Technology Limited, Pfizer, Inc.
    Inventors: Peter Francis Leadlay, James Staunton, Jesus Cortes, Hamish Alastair Irvine McArthur
  • Patent number: 7067286
    Abstract: Recombinant host cells of the suborder Cystobacterineae, genus Stizmatella, containing recombinant expression vectors that encode heterologous epothilone polyketide synthase (PKS) genes and can produce epothilones at high levels are provided.
    Type: Grant
    Filed: July 8, 2002
    Date of Patent: June 27, 2006
    Assignee: Kosan Biosciences, Inc.
    Inventors: Bryan Julien, Leonard Katz, Chaitan Khosla
  • Patent number: 7049100
    Abstract: A multiple-plasmid system for heterologous expression of polyketides facilitates combinatorial biosynthesis. The method can be extended to any modular polyketide synthase (PKS) or non-ribosomal peptide synthase (NRPS) and has the potential to produce thousands of novel natural products, including ones derived from further modification of the PKS or NRPS products by tailoring enzymes.
    Type: Grant
    Filed: March 22, 2002
    Date of Patent: May 23, 2006
    Assignee: Kosan Biosciences Incorporated
    Inventors: Daniel V. Santi, Qun Xue, Gary Ashley
  • Patent number: 7033621
    Abstract: Processes for the production of isoflavones are described wherein plant material from plants of the genus leguminosae are contacted with water, an enzyme which cleaves isoflavone glycosides to the aglucone form and a C2-C10 organic solvent, so as to form a combination, incubating the combination for a time sufficient to allow isoflavones of the aglucone form to partition into the organic solvent component, and thereafter recovering isoflavones from the organic solvent component.
    Type: Grant
    Filed: April 11, 2000
    Date of Patent: April 25, 2006
    Assignee: Novogen, Inc.
    Inventors: Graham E. Kelly, Jiu Li Huang, Mark G. Deacon-Shaw, Mark A. Waring
  • Patent number: 7018814
    Abstract: Provided is a method of purifying a vancomycin from a fermentation broth of a microorganism containing vancomycin, including passing the fermentation broth of a microorganism containing vancomycin through a strong acid cation exchange resin, a weak base anion exchange resin, alumina and a hydrophobic absorbent resin sequentially.
    Type: Grant
    Filed: September 17, 2004
    Date of Patent: March 28, 2006
    Assignee: CJ Corporation
    Inventors: Ju Won Lee, Yun Taek Jung, Jung Woo Suh, Kwang Seob Lee
  • Patent number: 7011959
    Abstract: Recombinant E. coli host cells that comprise recombinant DNA expression vectors that drive expression of methylmalonyl CoA mutase from Propionibacterium shermanii or Streptomyces cinnamonensis as well as Propionibacterium shermanii epimerase can produce S-methylmalonyl CoA, a required substrate for the production of polyketides by most modular polyketide synthases and is not present in wild-type E. coli host cells.
    Type: Grant
    Filed: October 27, 2000
    Date of Patent: March 14, 2006
    Assignee: Kosan Biosciences, Inc.
    Inventors: Daniel Santi, Larry Peck, Linda Dayem, James Kealey
  • Patent number: 7001748
    Abstract: Linking sequences which modulate cross-talk between modules of Type I polyketide synthases have been identified. Thus, arbitrarily chosen modules can be mixed and matched by supplying the appropriate linkers to obtain desired polyketide synthases and new polyketides. The modules are provided suitable linkers so that the polyketide chain is passed from one module to the other in the correct sequence. Synthetic peptides which mimic linkers can be used to inhibit the synthesis of polyketides. Kinetic channeling, both intrapolypeptide and interpolypeptide, of diketide intermediates in a Type I polyketide synthase can occur.
    Type: Grant
    Filed: March 4, 2002
    Date of Patent: February 21, 2006
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Rajesh S. Gokhale, Stuart Tsuji, Chaitan Khosla
  • Patent number: 7001747
    Abstract: Nucleic acid molecules encoding at least part of a Type I polyketide synthase, and having a polylinker with multiple restriction enzyme sites in place of one or more PKS genes encoding enzymes associated with reduction, optionally further including nucleic acid incorporated into the polylinker, the further nucleic acid encoding one or more reductive enzymes; plasmids incorporating such nucleic acids; host cells transfected with such plasmids; methods relating thereto.
    Type: Grant
    Filed: July 6, 1999
    Date of Patent: February 21, 2006
    Assignees: Biotica Technology Limited, Pfizer, Inc.
    Inventors: Johannes Kellenberger, Peter Francis Leadlay, James Staunton, Kim Jonelle Stutzman-Engwall, Hamish Alastair Irvine McArthur
  • Patent number: 6998256
    Abstract: Methods are provided for purification of epothilone D and epothilone D analogs from epothilone producing cells such as, for example, Sorangium cellulosum and Myxococcus xanthus (recombinant). Epothilone can be purified from fermentation broth, for example by using resins, chromatography, and crystallization. Epothilone D can be crystallized from a binary solvent system in which water is the forcing solvent.
    Type: Grant
    Filed: September 19, 2001
    Date of Patent: February 14, 2006
    Assignee: Kosan Biosciences, Inc.
    Inventor: Robert L. Arslanian
  • Patent number: 6984515
    Abstract: A polyketide or glycosylated polyketide which has the formula: wherein R* is methyl or ethyl; each of R1-R6 is methyl; X1 is OH or H; and/or X2 is=O, OH or H; X3 is OH or H; X4 is OH or H; a pi bond is present at positions 10-11, 8-9, 4-5 and/or 2-3; and wherein at least one of the following characteristics is present: X1 is H; X2 is OH or H; X3 is H; X4 is H; or a pi bond is present at positions 10-11, 8-9, 4-5 and/or 2-3.
    Type: Grant
    Filed: May 9, 2001
    Date of Patent: January 10, 2006
    Assignees: The LeLand Stanford Junior University, Kosan Biosciences, Inc.
    Inventors: Chaitan Khosla, Gary Ashley, Camilla Kao, Robert McDaniel
  • Patent number: 6960453
    Abstract: A hybrid type I polyketide synthase gene typically containing a starter module and a plurality of heterologous extender modules is used to synthesize novel polyketides. It is preferably under the control of a type II polypolyketide synthase promoter e.g. act I of S. coelicolor.
    Type: Grant
    Filed: July 4, 1997
    Date of Patent: November 1, 2005
    Assignee: Biotica Technology Limited
    Inventors: Peter Francis Leadlay, James Staunton, Jesus Cortes
  • Patent number: 6939691
    Abstract: The use of enzymes that catalyze the production of starter and extender units for polyketides in E. coli and Streptomyces is described; these enzymes include malonyl CoA decarboxylase (MatA), malonyl CoA synthetase (MatB), and a malonate transporter (MatC) as well as proprionyl CoA carboxylase (pcc). The matBC gene from Streptomyces coelicolor, the matABC genes from Rhizobium trifoli, and the pccB and accA2 from Streptomyces coelicolor are useful in specific embodiments of the claimed invention. These enzymes may be used to enhance the yield of polyketides that are natively produced or polyketides that are rationally designed. By using these techniques, the synthesis of a complete polyketide has been achieved in E. coli in the presence of a phosphopantetheinyl transferase, such as sfp from Bacillus subtilis. This achievement permits a host organism with desirable characteristics to be used in the production of such polyketides and to assess the results of gene shuffling.
    Type: Grant
    Filed: October 13, 2000
    Date of Patent: September 6, 2005
    Assignee: Board of Trustees of the Leland Stanford Junior University
    Inventors: Chaitan Khosla, Blaine Pfeifer
  • Patent number: 6927057
    Abstract: Combinatorial libraries of polyketides can be obtained by suitable manipulation of a host modular polyketide synthase gene cluster such as that which encodes the PKS for erythromycin. The combinatorial library is useful as a source of pharmaceutically active compounds. In addition, novel polyketides and antibiotics are prepared using this method.
    Type: Grant
    Filed: May 16, 2001
    Date of Patent: August 9, 2005
    Assignees: Kosan Biosciences, The Board of Trustees of the Leland Stanford Junior University
    Inventors: Chaitan Khosla, Gary Ashley, Camilla M. Kao, Robert McDaniel
  • Patent number: 6921650
    Abstract: Recombinant nucleic acids that encode all or a portion of the epothilone polyketide synthase (PKS) are used to express recombinant PKS genes in host cells for the production of epothilones, epothilone derivatives, and polyketides that are useful as cancer chemotherapeutics, fungicides, and immunosuppressants.
    Type: Grant
    Filed: November 28, 2000
    Date of Patent: July 26, 2005
    Assignee: Kosan Biosciences, Inc.
    Inventors: Bryan Julien, Leonard Katz, Chaitan Khosla, Li Tang, Rainer Ziermann
  • Patent number: 6902913
    Abstract: Recombinant DNA compounds that encode all or a portion of the narbonolide polyketide synthase are used to express recombinant polyketide synthase genes in host cells for the production of narbonolide, narbonolide derivatives, and polyketides that are useful as antibiotics and as intermediates in the synthesis of compounds with pharmaceutical value.
    Type: Grant
    Filed: February 22, 2001
    Date of Patent: June 7, 2005
    Assignee: Kosan Biosciences, Inc.
    Inventors: Melanie C. Betlach, Mary Betlach, Robert McDaniel, Li Tang
  • Patent number: 6902925
    Abstract: The present invention is a process for selective production of beauveriolide I substance or beauveriolide III substance, in which a beauveriolide producing microorganism strain FO-6979 or mutant thereof is cultured in a medium for fungi added with specific amino acid in order to produce beauveriolide I substance or beauveriolide III substance selectively with high yield; beauveriolide I substance or beauveriolide III substance is accumulated selectively in the cultured mass; and beauveriolide I substance or beauveriolide III substance is collected selectively with high yield from said cultured mass.
    Type: Grant
    Filed: April 10, 2001
    Date of Patent: June 7, 2005
    Assignees: Gakkou Houjin Kitasato Gakuen, Japan Society for the Promotion of Science
    Inventors: Satoshi Omura, Hiroshi Tomoda
  • Patent number: 6884604
    Abstract: The present invention provides combinatorial methods for rapidly generating a diverse library of glycorandomized structures, comprising incubating one or more aglycons and a pool of NDP-sugars in the presence of a glycosyltransferase. The glycosyltransferase may be one that is associated with or involved in production of natural secondary metabolites, or one which is putatively associated with or involved in production of natural secondary metabolites. The glycosyltransferase may show significant flexibility with respect to its NDP-sugar donors and/or its aglycons. NDP-sugar donors may be commercially available, or may be produced by utilizing mutant or wild type nucleotidyltransferases significant flexibility with respect to their substrates.
    Type: Grant
    Filed: April 1, 2002
    Date of Patent: April 26, 2005
    Assignee: Sloan-Kettering Institute for Cancer Research
    Inventor: Jon S. Thorson
  • Patent number: 6858411
    Abstract: Recombinant nucleic acids that encode all or a portion of the epothilone polyketide synthase (PKS) are used to express recombinant PKS genes in host cells for the production of epothilones, epothilone derivatives, and polyketides that are useful as cancer chemotherapeutics, fungicides, and immunosuppressants.
    Type: Grant
    Filed: November 28, 2000
    Date of Patent: February 22, 2005
    Assignee: Kosan Biosciences, Inc.
    Inventors: Bryan Julien, Leonard Katz, Chaitan Khosla, Li Tang, Rainer Ziermann
  • Patent number: 6858404
    Abstract: Nucleic acid molecules are isolated from Sorangium cellulosum that encode polypeptides necessary for the biosynthesis of epothilone. Disclosed are methods for the production of epothilone in recombinant hosts transformed with the genes of the invention. In this manner, epothilone can be produced in quantities large enough to enable their purification and use in pharmaceutical formulations such as those for the treatment of cancer.
    Type: Grant
    Filed: November 13, 2001
    Date of Patent: February 22, 2005
    Assignee: Novartis AG
    Inventors: Thomas Schupp, James Madison Ligon, Istvan Molnar, Ross Zirkle, Devon Dawn Cyr, Jörn Görlach
  • Patent number: 6846654
    Abstract: A system for detecting physical or chemical changes in an environment is disclosed. The system comprises means for conducting a chemical reaction; an active biological molecule whose physiological function is noncatalytic which is capable of catalyzing a chemical reaction wherein at least one reactant is converted to one product; and means for sensing and processing information relating to changes in said environment. A method for detecting physical or chemical changes in an environment is also disclosed.
    Type: Grant
    Filed: July 9, 1993
    Date of Patent: January 25, 2005
    Assignee: IGEN International, Inc.
    Inventors: Gary F. Blackburn, Charles Durfor, Michael J. Powell, Richard J. Massey
  • Patent number: 6838265
    Abstract: Generic overproduction host cells can be used to produce any polyketide and obviate the need for performing conventional strain improvement.
    Type: Grant
    Filed: May 1, 2001
    Date of Patent: January 4, 2005
    Assignee: Kosan Biosciences, Inc.
    Inventors: Daniel Santi, Robert McDaniel, Li Tang, Chaitan Khosla
  • Publication number: 20040266701
    Abstract: A novel family of cyclic polyene natural products isolated from marine actinomycete strain CNQ140 is provided. This novel strain of actinomycetes was obtained from a previously unstudied population of marine actinomycetes that reside in sediments off La Jolla, Calif. Compounds derived from strain CNQ140 have been characterized as having a cyclic polyene-polyol structure; a molecular weight from about 996 to about 1010 in the core ring structure; and at least 58 carbons and at least 14 oxygens. The invention compounds have antitumor and/or anti-microbial activity.
    Type: Application
    Filed: June 21, 2004
    Publication date: December 30, 2004
    Applicant: The Regents of the University of California
    Inventors: William H. Fenical, Paul R. Jensen, Hak Cheol Kwon
  • Patent number: 6828126
    Abstract: The heterologous expression of the oleandomycin polyketide synthase (OlePKS) in Streptomyces lividans, produces 8,8 a-deoxyoleandolide, an aglycone precursor of oleandomycin. The co-expression with deoxyerythronolide B synthase (DEBS) in S. lividans of the P450 monooxygenase OleP produces 8,8 a-dihydroxy-6-deoxyerythonolide B and other derivatives that are precursors to important macrolide antibiotics.
    Type: Grant
    Filed: November 16, 2001
    Date of Patent: December 7, 2004
    Assignee: Kosan Biosciences, Inc.
    Inventor: Robert McDaniel
  • Publication number: 20040235119
    Abstract: The invention relates to a method for the production of phospholipids of general formula (I) with the exclusive aid of phospholipase D from a phospholipid mixture and without using organic solvents, wherein phosphatidyl acid is produced in an aqueous, unbuffered phase with phospholipase D and at least one bivalent metal ion in a first step and at least one phospholipid of general formula (I) is produced from the phosphatidyl acid having at least one compound of general formula (II) R3—OH in a second step. Phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositeand/or phosphatidylglycerine are obtained as products. In another embodiment of the invention, the PLD is identical or different in both steps of said method, wherein in the latter case the pH values for the first and second steps of the method are different, said values lying particularly between 6.5 and 8.0, especially between 5.0 and 7.5.
    Type: Application
    Filed: February 26, 2004
    Publication date: November 25, 2004
    Inventors: Hans-Ulrich Hoppe, Firk Bokenkamp, Sinian Huang
  • Publication number: 20040219645
    Abstract: The complete sequence of the gene cluster for the monensin type I polyketide synthase, from S. cinnamonensis, is provided. Thus variant polyketides containing monensin-derived elements can be genetically engineered. Furthermore there are novel features, e.g. a regulatory protein mon RI, which are of wide utility.
    Type: Application
    Filed: May 6, 2002
    Publication date: November 4, 2004
    Inventors: Peter Francis Leadley, James Staunton, Mark Yan Oliynyk
  • Patent number: 6808903
    Abstract: Subject of the invention is a process for the preparation of a compound of formula (I) in which R1-R9 represent, independently of each other hydrogen a substituent; m is 0, 1 or 2; n is 0, 1, 2 or 3; and the bonds marked with A, B, C, D, E and F indicate, independently of each other, that two adjacent carbon atoms are connected by a double bond, a single bond, a single bond and an epoxide bridge, or a single bond and a methylene bridge, including, where applicable, an E/Z isomer, a mixture of E/Z isomers, and/or a tautomer thereof, in each case in free form or in salt form, which process comprises I) bringing a compound of formula (II); wherein R1-R7, m, n, A, B, C, D, E and F have the same meanings as given for formula (I) above, into contact with a biocatalyst that is capable of specifically oxidising the alcohol at position 4″ in order to form a compound of formula (III), in which R1, R2, R3, R4, R5, R6, R7, m, n, A, B, C, D, E and F have the meanings given for formula (I); and 2) reacting the compou
    Type: Grant
    Filed: May 8, 2002
    Date of Patent: October 26, 2004
    Assignee: Syngenta Participations AG
    Inventors: Johannes Paul Pachlatko, Thomas Pitterna, Volker Jungmann
  • Publication number: 20040166567
    Abstract: The invention provides strategies, methods, vectors, reagents, and systems for production of synthetic genes, production of libraries of such genes, and manipulation and characterization of the genes and corresponding encoded polypeptides. In one aspect, the synthetic genes can encode polyketide synthase polypeptides and facilitate production of therapeutically or commercially important polyketide compounds.
    Type: Application
    Filed: September 26, 2003
    Publication date: August 26, 2004
    Inventors: Daniel V. Santi, Ralph C. Reid, Sarah J. Kodumal, Sebastian Jayaraj
  • Publication number: 20040146992
    Abstract: A method for the production of a polyketide by fermentation comprising the steps of growing a culture of a polyketide-producing organism at a pH value conducive to cell growth for a time sufficient to generate the producing culture, lowering the pH of the culture to a value conducive to polyketide product stability, continuing the fermentation until a maximal titer of polyketide is achieved, and optionally extracting the polyketide from the culture.
    Type: Application
    Filed: November 12, 2003
    Publication date: July 29, 2004
    Inventors: Rika Regentin, Ruchir P. Desai
  • Patent number: 6689611
    Abstract: The present invention is directed to compositions and methods for producing avermectins, and is primarily in the field of animal health. The present invention relates to the identification and characterization of two novel genes, herein referred to as the aveR1 and aveR2 genes, that are involved in regulating avermectin polyketide synthase (PKS) expression and avermectin biosynthesis in Streptomyces avermitilis. The present invention is based on the discovery that inactivation of these genes results in an increase in the amount of avermectin produced by S. avermitilis.
    Type: Grant
    Filed: November 16, 2000
    Date of Patent: February 10, 2004
    Assignee: Pfizer Inc.
    Inventors: Kim J. Stutzman-Engwall, Brenda S. Price
  • Publication number: 20040023343
    Abstract: Spinosyn biosynthetic genes, spinosyn producing microorganisms transformed with the biosynthetic genes, methods using the biosynthetic genes to increase production of spinosyn insecticidal macrolides, and methods using the genes or fragments thereof to change the products produced by spinosyn-producing microorganisms.
    Type: Application
    Filed: December 23, 2002
    Publication date: February 5, 2004
    Inventors: Richard H. Baltz, M. Christine Broughton, Kathryn P. Crawford, Krishnamurthy Madduri, Donald J. Merlo, Patti J. Treadway, Jan R. Turner, Clive Waldron
  • Publication number: 20040009560
    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.
    Type: Application
    Filed: June 11, 2003
    Publication date: January 15, 2004
    Applicant: Pfizer Inc.
    Inventors: Kim J. Stutzman-Engwall, Chen Yan, Claes Gustafsson, Anke Krebber, Jeremy Minshull, Sun Ai Raillard
  • Publication number: 20040005672
    Abstract: Recombinant host cells that comprise recombinant DNA expression vectors that drive expression of a product and a precursor for biosynthesis of that product can be used to produce useful products such as polyketides in host cells that do not naturally produce the product or produce the product or precursor at low levels due to the absence of the precursor or the presence of the precursor in rate limiting amounts.
    Type: Application
    Filed: February 21, 2003
    Publication date: January 8, 2004
    Inventors: Daniel V. Santi, Chaitan Khosla
  • Publication number: 20030235892
    Abstract: Recombinant host cells that comprise recombinant DNA expression vectors that drive expression of a product and a precursor for biosynthesis of that product can be used to produce useful products such as polyketides in host cells that do not naturally produce the product or produce the product at low levels due to the absence of the precursor or the presence of the precursor in rate limiting amounts.
    Type: Application
    Filed: June 27, 2003
    Publication date: December 25, 2003
    Inventors: Leonard Katz, Peter Revill
  • Publication number: 20030232415
    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.
    Type: Application
    Filed: June 11, 2003
    Publication date: December 18, 2003
    Applicant: Pfizer Inc.
    Inventors: Kim J. Stutzman-Engwall, Yan Chen, Claes Gustafsson, Anke Krebber, Jeremy Minshull, Sun Ai Raillard
  • Publication number: 20030186899
    Abstract: Macrolide compounds produced by culturing Saccharopolyspora species LW107129 (NRRL 30141) have insecticidal and acaricidal activity and are useful intermediates for preparing spinosyn analogs.
    Type: Application
    Filed: August 13, 2002
    Publication date: October 2, 2003
    Inventors: Paul Lewer, Donald R. Hahn, Laura L. Karr, Paul R. Graupner, Jeffrey R. Gilbert, Thomas V. Worden, Raymond C. Yao, Dennis W. Norton
  • Publication number: 20030175901
    Abstract: Host cells comprising recombinant vectors encoding the FK-520 polyketide synthase and FK-520 modification enzymes can be used to produce the FK-520 polyketide. Recombinant DNA constructs comprising one or more FK-520 polyketide synthase domains, modules, open reading frames, and variants thereof can be used to produce recombinant polyketide synthases and a variety of different polyketides with application as pharmaceutical and veterinary products.
    Type: Application
    Filed: August 27, 2001
    Publication date: September 18, 2003
    Inventors: Christopher Reeves, Daniel Chu, Chaitan Khosla, Daniel Santi, Kai Wu
  • Publication number: 20030170725
    Abstract: Combinatorial libraries of polyketides can be obtained by suitable manipulation of a host modular polyketide synthase gene cluster such as that which encodes the PKS for erythromycin. The combinatorial library is useful as a source of pharmaceutically active compounds. In addition, novel polyketides and antibiotics are prepared using this method.
    Type: Application
    Filed: August 6, 2002
    Publication date: September 11, 2003
    Inventors: Chaitan Khosla, Camilla M. Kao
  • Publication number: 20030166165
    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.
    Type: Application
    Filed: February 10, 2003
    Publication date: September 4, 2003
    Inventors: Kim J. Stutzman-Engwall, Anke Krebber, Claes Gustafsson, Jeremy S. Minshull, Sun Ai Raillard, Seran Kim, Yan Chen
  • Publication number: 20030162262
    Abstract: Recombinant DNA compounds that encode all or a portion of the narbonolide polyketide synthase are used to express recombinant polyketide synthase genes in host cells for the production of narbonolide, narbonolide derivatives, and polyketides that are useful as antibiotics and as intermediates in the synthesis of compounds with pharmaceutical value.
    Type: Application
    Filed: May 29, 2002
    Publication date: August 28, 2003
    Inventors: Gary Ashley, Melanie C. Betlach, Mary Betlach, Robert McDaniel, Li Tang
  • Publication number: 20030157652
    Abstract: The nucleic acid and amino acid sequences of &agr;1, &agr;2, &bgr; and &egr; subunits of acetyl-CoA carboxylase (ACCase) from Streptomyces coelicolor are provided. This subunit structure differs from that of known acyl carboxylases. Materials and methods are provided of increasing ACCase activity and production of secondary metabolites (such as polyketides and especially antibiotics) by causing expression in Streptomyces of such nucleic acid.
    Type: Application
    Filed: October 23, 2001
    Publication date: August 21, 2003
    Inventors: Hugo Cesar Gramajo, Eduardo Jose Rodriguez
  • Publication number: 20030153053
    Abstract: Ketoreductase (KR) domains of modular polyketide synthase (PKS) enzymes can be inactivated by one or more point mutations in the domain. Replacement or insertion of a KR domain can be used to introduce a cis or trans double bond into a polyketide by appropriate selection or inactivation of the type of KR domain that codes for a particular stereochemical configuration of a hydroxyl moiety. Inactivation of a DH domain can be used to produce a polyketide having a hydroxyl moiety with a desired stereochemical configuration.
    Type: Application
    Filed: August 6, 2002
    Publication date: August 14, 2003
    Inventor: Ralph Reid
  • Publication number: 20030148469
    Abstract: Combinatorial libraries of polyketides can be obtained by suitable manipulation of a host modular polyketide synthase gene cluster such as that which encodes the PKS for picromycin. The combinatorial library is useful as a source of pharmaceutically active compounds. In addition, novel polyketides and antibiotics are prepared using this method.
    Type: Application
    Filed: July 22, 2002
    Publication date: August 7, 2003
    Inventors: Gary Ashley, Melanie C. Betlach, Mary Betlach, Robert McDaniel, Li Tang
  • Publication number: 20030143666
    Abstract: The present invention relates to isolated genetic sequences encoding proteins which direct the biosynthesis of the antibiotic everninomicin in Micromonospora carbonacea. The isolated biosynthetic gene cluster serves as a substrate for bioengineering of antibiotic structures.
    Type: Application
    Filed: January 26, 2001
    Publication date: July 31, 2003
    Inventors: Alfredo Staffa, Emmanuel Zazopoulos, Stephane Mercure, Piotr Peter Nowacki, Chris M. Farnet
  • Publication number: 20030138879
    Abstract: The invention pertains to isolated phosphopantetheinyl transferases, such as the E. coli acyl carrier protein synthase, which transfer a phosphopantetheinyl group onto a substrate. The enzyme can be purified from a natural source, produced recombinantly, or synthetically. Accordingly, the invention provides compositions and kits including phosphopantetheinyl transferases and host cells expressing phosphopantetheinyl transferases. The invention also provides nucleic acids encoding phosphopantetheinyl transferases and vectors comprising such nucleic acids. The invention further provides methods for phosphopantetheinylating a substrate in vitro or in vivo and methods for producing antibiotics in vitro or in vivo.
    Type: Application
    Filed: September 30, 2002
    Publication date: July 24, 2003
    Applicant: President and Fellows of Harvard College
    Inventors: Ralph H. Lambalot, Amy M. Gehring, Ralph Reid, Christopher T. Walsh
  • Publication number: 20030138841
    Abstract: Genetic engineering of the erythromycin polyketide synthase genes to effect combinatorial alterations of catalytic activities in the biosynthetic pathway can be used to generate a library of macrolides impractical to produce by chemical methods. The library includes examples of analogs with one, two and three altered carbon centers of the polyketide products.
    Type: Application
    Filed: April 22, 2002
    Publication date: July 24, 2003
    Inventor: Robert McDaniel
  • Publication number: 20030124679
    Abstract: The invention provides compositions, including pharmaceuticals, comprising glycosylated kinamycins. The compositions and methods of the invention can be used to treat infections, i.e., as antibiotics, and as anti-tumor agents. The compositions of the invention can also act as act as electrophilic azo-coupling agents in vitro or in vivo. The invention also provides enzymes capable of generating kinamycin, nucleic acids that encode them, antibodies that bind to them, and methods for making and using them.
    Type: Application
    Filed: June 27, 2002
    Publication date: July 3, 2003
    Inventors: Jay M. Short, Ashish Paradkar, Mustafa Varoglu, Eric J. Mathur
  • Publication number: 20030124680
    Abstract: Three distinct primary regions of acyltransferase (AT) domains of modular polyketide synthases (PKS) can be changed by site-specific mutagenesis of the corresponding coding sequences to change the specificity of the domain and the structure of the polyketide produced by the PKS.
    Type: Application
    Filed: August 7, 2002
    Publication date: July 3, 2003
    Inventors: Christopher Reeves, Robert McDaniel, Ralph Reid