Abstract: Novel polyketides and novel methods of efficiently producing both new and known polyketides, using recombinant technology, are disclosed. In particular, a novel host-vector system is described which is used to produce polyketide synthases which in turn catalyze the production of a variety of polyketides.

Abstract: Linking sequence 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. In addition, the role of protein-protein interactions between a donor acryl carrier protein (ACP) domain and a downstream ketosynthase (KS) domain and enzyme-substrate interactions in the channeling of intermediates between polyketide synthase modules and between a polyketide synthase module and a NRPS module has been identified.

Abstract: Transglutaminase inhibitors and methods of use thereof are provided.

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: A ministering an effective dose of a tTGase inhibitor to a Celiac or dermatitis herpetiformis patient reduces the toxic effects of toxic gluten oligopeptides, thereby attenuating or eliminating the damaging effects of gluten.

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: 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: Administering an effective dose of glutenase to a Celiac or dermatitis herpetiformis patient reduces levels of toxic gluten oligopeptides, thereby attenuating or eliminating the damaging effects of gluten.

Abstract: Methods and materials are provided for E. coli host cells containing an expression system for producing NDP 6-deoxy-sugar, which may also comprise an expression system for expressing 6-deoxyglycosyl transferase and/or an expression system for producing a polyketide and/or polyketide oxidation enzymes.

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

Abstract: Screening methods and methods of treatment taking advantage of the mode of action of apoptolidin and its analogs are described.

Abstract: Compounds according to formula I wherein m is 0 or 1; X is and R1, R2, R3 R4, and R5 are as defined herein, are useful as anti-infective agents.

Abstract: Novel polyketides and novel methods of efficiently producing both new and known polyketides, using recombinant technology, are disclosed. In particular, a novel host-vector system is described which is used to produce polyketide synthases which in turn catalyze the production of a variety of polyketides.

Abstract: Celiac Sprue and/or dermatitis herpetiformis arc treated by interfering with HLA binding of immunogenic gluten peptides. The antigenicity of gluten oligopeptides and the ill effects caused by an immune response thereto are decreased by administration of an HLA-binding peptide inhibitor. Such inhibitors are analogs of immunogenic gluten peptides and (i) retain the ability to bind tightly to HLA molecules; (ii) retain the protcolytic stability of these peptides; but (iii) are unable to activate disease-specific T cells.

Abstract: Administering an effective dose of glutenase to a Celiac or dermatitis herpetiformis patient reduces levels of toxic gluten oligopeptides, thereby attenuating or eliminating the damaging effects of gluten.

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 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: The substrate specificity of modular polyketide synthases is altered by mutating or replacing acyltransferase regions thereof.