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

Abstract: The rapamycin gene cluster is an example of a gene cluster which includes a gene (rapL) leading to the formation of a precursor compound (pipecolic acid, in this case) which is required for inclusion in the larger product (rapamycin) produced by the enzymes encoded by the cluster. We have produced a mutant strain containing a rapamycin gene cluster in which the rapL gene is disabled. The strain does not naturally produce rapamycin but does so if fed with pipecolic acid. By feeding with alternative carboxylic acids we have produced variants of rapamycins. Tests have shown biological activity.

Abstract: Recombinant Escherichia 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 not present in wild-type E. coli host cells.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Abstract: Generic overproduction host cells can be used to produce any polyketide and obviate the need for performing conventional strain improvement.

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.

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.

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.

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.

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

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.

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.

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.

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.

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

Abstract: 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.

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.

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

Abstract: Macrolide compounds produced by culturing Saccharopolyspora species LW107129 (NRRL 30141) have insecticidal and acaricidal activity and are useful intermediates for preparing spinosyn analogs.

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.

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.

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

Abstract: 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.

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.

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.

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.

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.

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.