Chromaxome Corporation

Michigan State University

Terragen Discovery Inc.

Paul Brian

Todd C Peterson

Lyndon M Foster

Katie A Thompson

Nicole Marie Nasby

Wendy C Champness

Todd B Anderson

The present invention relates to a novel drug discovery system for generating molecular diversity. The system provides methods for subjecting the genetic materials from a plurality of species of organisms to homologous or homeologous recombination to create novel genes and metabolic pathways. The recombined genetic materials are cloned to form recombined combinatorial gene expression libraries. Methods for screening such gene expression libraries containing recombined genes and metabolic pathways for novel activities and compounds are also provided.

Methods for generating and screening novel metabolic pathways

A recombinant Streptomyces sp. which exhibits hyperproduction of an antibiotic, particularly actinorhodin and undecylprodigiosin, as a result of interruption of the absA homologous locus of chromosomal DNA (SEQ ID NO:1) is described. The gene is thought to encode a histidine kinase and a response regulator. The preferred bacterium is Streptomyces coelicolor. It is preferred to interrupt the absA1 gene with ermE DNA.

Method, DNA and bacteria for hyperproduction of an antibiotic due to

The present invention relates to a novel drug discovery system for generating and screening molecular diversity. The system provides methods for mixing and cloning genetic materials from a plurality of species of organisms in combinatorial gene expression libraries to generate novel metabolic pathways and classes of compounds. The system also involves methods for pre-screening or identifying for host organisms containing a library that are capable of generating such novel pathways and compounds. The host organisms may be useful in drug screening for particular diseases, and in commercial production of compounds of interest. The methods of the invention are also useful in preserving the genomes of organisms that are known or prospective sources of drugs.

The present invention relates to a novel drug discovery system for generating and screening molecular diversity. The system provides methods for mixing and cloning genetic materials from a plurality of species of organisms in combinatorial gene expression libraries to generate novel metabolic pathways and classes of compounds. The system also provides mobilizable combinatorial gene expression libraries that can be transferred from one species of host organism to another for expression. Also provided are specialized cloning vectors for making mobilizable gene expression libraries. The system also involves methods for pre-screening or identifying for host organisms containing a library that are capable of generating such novel pathways and compounds.

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San Diego, CA, United States of America

Paul Brian