Kosan Biosciences Incorporated

Ralph C Reid

Zhihao Hu

Robert G McDaniel

Andreas W Schirmer

Bryan Julien

Christopher Reeves

Richard C Hutchinson

Andreas Rascher

Chaitan Khosla

Daniel V Santi

Leonard Katz

John R Carney

Michael A Siani

Yong Li

C Richard Hutchinson

Hugo Menzella

Hugo Gramajo

The invention provides novel compounds that may be used as intermediates in the preparation of epothilones, epothilone analogs and derivative, as well as new synthetic methods for producing the intermediates and products.

Methods of making epothilones

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.

Biosynthetic gene cluster for leptomycins

Methods for the computational analysis of polyketides and the computer-assisted design of PKS genes are facilitated by representing the structure of a polyketide and/or a PKS gene that encodes the PKS that produces the polyketide by alphanumeric symbols that facilitates computer assisted analysis. A database of polyketides and corresponding PKS genes that can be rapidly searched and information extracted for a variety of applications, including the design and specification of PKS genes via the recombining of modules or portions of modules or sets of modules from already known and available PKS genes.

Design of polyketide synthase genes

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.

Recombinant polynucleotides encoding pro-geldanamycin producing polyketide synthases and accessory proteins, and uses thereof

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

Recombinant genes for polyketide modifying enzymes

The sequence of the disorazole polyketide synthase protein gene is disclosed. 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.

Polynucleotides encoding disorazole polyketide synthase polypeptides

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.

Biosynthetic gene cluster for ambruticins and the encoded proteins

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.

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San Rafael, CA, United States of America

Ralph C Reid