Schering Corporation

Thomas J Hosted

Ann C Horan

Tim X Wang

Marvin L Bayne

Scott Walker

This invention is directed to nucleic acids which encode the proteins that direct the synthesis of the orthosomycin everninomicin and to use of the nucleic acids and proteins to produce compounds exhibiting antibiotic activity based on the everninomycin structure. The DNA sequence for the gene clusters responsible for encoding everninomicin biosynthetic genes, which provide the machinery for producing everninomicin, are provided. Thus, this invention provides the nucleic acid sequences needed to synthesize novel everninomicin-related compounds based on everninomicin, arising from modifications of the DNA sequence designed to change glycosyl and modified orsellinic acid groups contained in everninomicin. Asite-specific integrase gene is also provided, which can be incorporated in a vector for integration into any actinomycete, and, particularly into. Thus, the invention further provides methods for introducing heterologous genes into an actinomycete chromosome using this particular vector.

Everninomicin biosynthetic genes

The present invention comprises responsive promoters along with screening methods which make use of the promoters in order to identify anti-fungal substances.

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Everninomicin biosynthetic proteins

Plasmid genes fromvar.ATCC39149 pMLP1 have been isolated cloned, sequenced and functionally identified. These genes have been used to create vectors which integrate in a site-specific manner into the host chromosome of actinomycete species.

This invention is directed to nucleic acids which encode the proteins that direct the synthesis of the orthosomycin everninomicin and to use of the nucleic acids and proteins to produce compounds exhibiting antibiotic activity based on the everninomycin structure. The DNA sequence for the gene clusters responsible for encoding everninomicin biosynthetic genes, which provide the machinery for producing everninomicin, are provided. Thus, this invention provides the nucleic acid sequences needed to synthesize novel everninomicin-related compounds based on everninomicin, arising from modifications of the DNA sequence designed to change glycosyl and modified orsellinic acid groups contained in everninomicin. A.site-specific integrase gene is also provided, which can be incorporated in a vector for integration into any actinomycete, and, particularly into. Thus, the invention further provides methods for introducing heterologous genes into an actinomycete chromosome using this particular vector.

Plasmid genes from pMR2 have been isolated, cloned, sequenced and functionally identified. These genes have been used to create vectors which can be used to express actinomycete genes, manipulate metabolic pathways and produce useful gene products such as hybrid antibiotics.

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Summit, NJ, United States of America

Thomas J Hosted