Ecopia Biosciences, Inc.

Thallion Pharmaceuticals Inc.

Cubist Pharmaceuticals, Incorporated

Emmanuel Zazopoulos

Chris M. Farnet

Alfredo Staffa

Chris M Farnet

Chirs M Farnet

The present invention relates to isolated genetic sequences encoding nonribosomal peptide synthetase (NRPS) proteins which direct the biosynthesis of the antibiotic ramoplanin in microorganisms such assp. The isolated gene sequences serve as substrates for bioengineering of antibiotic structures.

Gene encoding a nonribosomal peptide synthetase for the production of ramoplanin

Five protein families cooperate to form the warhead structure that characterizes enediyne compounds, both chromoprotein enediynes and non-chromoprotein enediynes. The protein families include a polyketide synthase and thioesterase protein which form a polyketide synthase catalytic complex involved in warhead formation in enediynes. Genes encoding a member of each of the five protein families are found in all enediyne biosynthetic loci. The genes and proteins may be used in genetic engineering applications to design new enediyne compounds and in methods to identify new enediyne biosynthetic loci.

Nucleic acids encoding an enediyne polyketide synthase complex

Genes and proteins involved in the biosynthesis of benzodiazepines by microorganisms, including the genes and proteins forming the biosynthetic loci for the benzodiazepine anthramycin fromsubsp.. The genes and proteins allow direct manipulation of benzodiazepines and related chemical structures via chemical engineering of the enzymes involved in the biosynthesis of anthramycin.

Nucleic acid fragment encoding an NRPS for the biosynthesis of anthramycin

A method for identifying gene cluster is disclosed. The method may be used for identifying gene clusters involved in the biosynthesis of natural products. A small insert library of DNA fragments of genomic DNA and a large insert library of DNA fragments of genomic DNA are prepared. Fragments in the small insert library are sequenced and compared by homology comparison under computer control to a database containing genes, gene fragments or proteins known to be involved in the biosynthesis of microbial natural products. Fragments having similar structure to genes, gene fragments or proteins known to be involved in the biosynthesis of naturally occurring metabolites are used as probes to screen the large insert library of genomic DNA to detect gene clusters involved in the biosynthesis of microbial natural products.

High throughput method for discovery of gene clusters

Genes and proteins involved in the biosynthesis of lipopeptides by microorganisms, in particular the nucleic acids forming the biosynthetic locus for the A54145 lipopeptide fromand the A54145-like lipopeptide from. These nucleic acids can be used to make expression constructs and transformed host cells for the production of lipopeptides. The genes and proteins allow direct manipulation of lipopeptides and related chemical structures via chemical engineering of the proteins involved in the biosynthesis of A54145.

Genes and proteins involved in the biosynthesis of lipopeptides

Genes and proteins involved in the biosynthesis of benzodiazepines by microorganisms, including the genes and proteins forming the biosynthetic loci for the benzodiazepine anthramycin fromsubsp.including non-ribosomal peptide synthetases (NRPS). The genes and proteins allow direct manipulation of benzodiazepines and related chemical structures via chemical engineering of the enzymes involved in the biosynthesis of anthramycin.

The present invention relates to an isolated genetic sequence encoding a nonribosomal peptide synthetase (NRPS) protein which directs the biosynthesis of the antibiotic ramoplanin in microorganisms such assp. The isolated gene sequence serves as a substrate for bioengineering of antibiotic structures.

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Saint-Laurent, Canada

Alfredo Staffa