Kosan Biosciences Incorporated

Kosam Biosciences, Inc.

Kason Biosciences, Inc.

Li Tang

Chaitan Khosla

Leonard Katz

Bryan Julien

Robert G McDaniel

Rainer Ziermann

Gary W Ashley

Mary C Betlach

Melanie C Betlach

Brian Walter Metcalf

Daniel V Santi

John R Carney

Yong Li

Robert L Arslanian

Sanjay Krishnakant Shah

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 present invention provides bioconversion methods for making epothilone analogs. These analogs differ from the starting material by the addition of one or more hydroxyl groups or by the addition of an epoxide. These compounds, in turn, can be further modified by chemical synthesis.

Epothilone compounds and methods for making the same

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.

Recombinant narbonolide polyketide synthase

This invention relates to compounds of formula (I)and to pharmaceutically acceptable salts and solvates thereof, wherein R, R, R, R, R, W, X, Y, and Ar are as defined herein. Compounds of formula (I) are useful in the treatment of diseases or conditions characterized by cellular hyperproliferation. This invention also relates to means for the preparation of compounds of formula (I); formulations containing compounds of formula (I); and methods for the use of said compounds and formulations in the treatment of a disease or condition characterized by cellular hyperproliferation, including cancer.

Epothilone derivatives and methods for making and using the same

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

Overproduction hosts for biosynthesis of polyketides

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

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.

Polyketide synthase genes from Streptomyces venezuelae

Recombinant methods and materials for producing epothilones C and D

Recombinant DNA compounds that encode all or a portion of the oleandolide polyketide synthase are used to express recombinant polyketide synthase genes in host cells for the production of oleandolide, oleandolide derivatives, and polyketides that are useful as antibiotics and motilides.

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Foster City, CA, United States of America

Li Tang