Abstract: Polypeptides and domains of leptomycin polyketide synthase and the nucleic acids encoding them are provided. Methods to prepare leptomycin, leptomycin analogs, and leptomycin derivatives are described, as are methods to prepare other polyketides using the nucleic acids encoding leptomycin polyketide synthase domains or modifying enzymes.

Abstract: Materials and methods to produce modified polyketides are disclosed. The biosynthesis, transfer and regulator genes for various sugars to effectuate polyketide modification are disclosed.

Abstract: The invention relates to recombinant polyketide synthase enzymes, polyketide modifying proteins, and other proteins involved in polyketide biosynthesis or function. The invention provides domains of geldanamycin and herbimycin polyketide synthases, polynucleotides that encode such enzymes, and to host cells in which such encoding polynucleotides can be advantageously expressed.

Abstract: Polypeptides and domains of leptomycin polyketide synthase and the nucleic acids encoding them are provided. Methods to prepare leptomycin, leptomycin analogs, and leptomycin derivatives are described, as are methods to prepare other polyketides using the nucleic acids encoding leptomycin polyketide synthase domains or modifying enzymes.

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.

Abstract: Resorcylic acid lactones having a C5-C6 cis double bond and a ketone at C7 and other compounds capable of Michael adduct formation are potent and stable inhibitors of a subset of protein kinases having a specific cysteine residue in the ATP binding site.

Abstract: Domains of ambruticin polyketide synthase and modification enzymes and polynucleotides encoding them are provided. Methods to prepare ambruticin in pharmaceutically useful quantities are described, as are methods to prepare ambruticin analogs and other polyketides using the polynucleotides encoding ambruticin synthase domains or modifying enzymes.

Abstract: Domains of jerangolid polyketide synthase and modification enzymes and polynucleotides encoding them are provided. Methods to prepare jerangolid in pharmaceutically useful quantities are described, as are methods to prepare jerangolid analogs and other polyketides using the polynucleotides encoding jerangolid synthase domains or modifying enzymes.

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: Domains of fostriecin polyketide synthase and modification enzymes and polynucleotides encoding them are provided. Methods to prepare fostriecin in pharmaceutically useful quantities are described, as are methods to prepare fostriecin analogs and other polyketides using the polynucleotides encoding fostriecin polyketide synthase domains or modifying enzymes.

Abstract: Polypeptides and domains of leptomycin polyketide synthase and the nucleic acids encoding them are provided. Methods to prepare leptomycin, leptomycin analogs, and leptomycin derivatives are described, as are methods to prepare other polyketides using the nucleic acids encoding leptomycin polyketide synthase domains or modifying enzymes.

Abstract: Domains of disorazole polyketide synthase and polynucleotides encoding them are provided. Methods to prepare disorazoles in pharmaceutically useful quantities are described, as are methods to prepare disorazole analogs and other polyketides using the polynucleotides encoding disorazole polyketide synthase domains or modifying enzymes.

Abstract: Materials and methods to produce modified polyketides are disclosed. The biosynthesis, transfer and regulator genes for various sugars to effectuate polyketide modification are disclosed.

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: 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.

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.

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.