Kosan Biosciences Incorporated

Monogram Biosciences, Inc.

Virologic, Inc.

Kosam Biosciences, Inc.

Rainer Ziermann

Bryan Julien

Chaitan Khosla

Leonard Katz

Li Tang

Gary W Ashley

Philip J Barr

Daniel V Santi

Neil T Parkin

Mary C Betlach

Claes Gustafsson

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

This invention relates to antiviral drug susceptibility and resistance tests to be used in identifying effective drug regimens for the treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), particularly treatment regimens including a protease inhibitor. The invention further relates to the means and methods of monitoring the clinical progression of HIV infection and its response to antiretroviral therapy using phenotypic or genotypic susceptibility assays.

Means and methods for monitoring protease inhibitor antiretroviral therapy and guiding therapeutic decisions in the treatment of HIV/AIDS

Hybrid and novel polyketide synthases and polyketides are produced by use of a multiple vector system. The combinatorial possibilities offered by placing the various catalytic activities of PKS systems on separate vectors permits the construction of improved libraries of PKS and polyketides. In addition, polyketides can be produced in hosts that ordinarily do not produce polyketides by supplying, along with an expression system for the desired PKS, an expression system for holo ACP synthase.

Production of polyketides in bacteria and yeast

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

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.

Sorangium polyketide synthases and encoding DNA therefor

Hybrid and novel polyketide synthases (PKSs) and polyketides are produced by use of a multiple vector system. The combinatorial possibilities offered by placing the various catalytic activities of PKS systems on separate vectors permits the construction of improved libraries of PKS and polyketides. In addition, polyketides can be produced in hosts that ordinarily do not produce polyketides by supplying, along with an expression system for the desired PKS, an expression system for holo acyl carrier protein (ACP) synthase.

Yields of polyketides produced in host cells such as Streptomyces can be increased by coexpression of the ptpA gene. The introduction of recombinant vectors encoding ptpA and polyketide synthase genes is more efficient and does not require methyl-free DNA if the host cell is a restriction/methylation deficient strain, such as,K4-114, K4-155, or K27-39.

Growing community of inventors

San Mateo, CA, United States of America

Rainer Ziermann