Kosan Biosciences Incorporated

Kosam Biosciences, Inc.

Kason Biosciences, Inc.

Bryan Julien

Chaitan Khosla

Leonard Katz

Li Tang

Rainer Ziermann

Ralph C Reid

Gary W Ashley

Claes Gustafsson

Mary C Betlach

Christopher Reeves

Peter J Licari

Scott Frykman

Hiroko Tsuruta

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.

Recombinant methods and materials for producing epothilone and epothilone derivatives

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

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.

Secondary metabolite congener distribution modulation

A transposon-based mutagenesis method for altering DNA inand otherhost cells is provided, along with vectors and transposases for use in the method.

Transposon-based transformation system

Recombinant host cells of the suborder Cystobacterineae, genus, containing recombinant expression vectors that encode heterologous epothilone polyketide synthase (PKS) genes and can produce epothilones at high levels are provided.

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Compounds of the invention include 14-mehtyl epothilone derivatives. More generally, preferred compounds of the invention are those that can be produced by altering the epothilone PKS genes as described herein and optionally by action of epothilone modification enzymes and/or by chemically modifying the resulting epothilones produces when those genes are expressed.

14-methyl epothilone derivatives

Recombinant Myxococcus host cell containing recombinant expression vectors containing epothilone polyketide synthase genes can produce epothilones C and D.

Myxococcus host cells for the production of epothilones

Recombinant methods and materials for producing epothilones C and D

Novel Sorangium polyketide synthases, and domains thereof, and polynucleotides encoding therefor. Additionally, chimeric polyketide synthases that include domains, or subsets of domains, patterned on said novel polyketide synthases. Methods to prepare polyketide combinatorial libraries are described, as are recombinant host cells in which polyketides are produced.

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Oakland, CA, United States of America

Bryan Julien