Thallion Pharmaceuticals Inc.

Ecopia Biosciences, Inc.

Cubist Pharmaceuticals, Incorporated

Thallion Pharmceuticals Inc.

James B. Mc Alpine

Emmanuel Zazopoulos

Chris M. Farnet

Alfredo Staffa

Brian O. Bachmann

Chris M Farnet

James B McAlpine

Brian O Bachmann

Mahmood Piraee

Arjun H Banskota

Nargis Ismail

Dan Sorensen

James B Mcalpine

The present invention provides cyclic hexadepsipeptides and their pharmaceutically acceptable salts, solvates and prodrugs, and methods for obtaining the compounds, by fermentation, optionally followed by post-biosynthesis chemical modification. The present invention further provides uses of cyclic hexadepsipeptides, and their pharmaceutically acceptable salts, solvates and prodrugs as pharmaceuticals, in particular to their use as antibacterial, antifungal or antineoplastic agents, and to pharmaceutical compositions comprising a cyclic hexadepsipeptide, or a pharmaceutically acceptable salt, solvate or prodrug thereof, together with a carrier.

Cyclic hexadepsipeptides, processes for their production and their use as pharmaceuticals

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

This invention relates to a novel farnesylated dibenzodiazepinone, named ECO-04601, its pharmaceutically acceptable salts and derivatives, and to methods for obtaining such compounds. One method of obtaining the ECO-04601 compound is by cultivation of a novel strain ofsp., 046-ECO11; another method involves expression of biosynthetic pathway genes in transformed host cells. The present invention further relates tosp. strain 046-ECO11, to the use of ECO-04601 and its pharmaceutically acceptable salts and derivatives as pharmaceuticals, in particular to their use as inhibitors of cancer cell growth, bacterial cell growth, mammalian lipoxygenase, and to pharmaceutical compositions comprising ECO-04601 or a pharmaceutically acceptable salt or derivative thereof. Finally, the invention relates to novel polynucleotide sequences and their encoded proteins, which are involved in the biosynthesis of ECO-04601.

Farnesyl dibenzodiazepinone and processes for its production

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

This invention relates to a new class of polyene polyketides, their pharmaceutically acceptable salts and derivatives, and to methods for obtaining the compounds. One method of obtaining these compounds is by cultivation of novel strains of; another method involves expression of biosynthetic pathway genes in transformed host cells. The present invention further relates to the novel strains ofused to produce these compounds, to the use of these compounds and their pharmaceutically acceptable salts and derivatives as pharmaceuticals, in particular to their use as inhibitors of fungal cell growth and cancer cell growth. The invention also relates to pharmaceutical compositions comprising these novel polyketides or a pharmaceutically acceptable salts or derivatives thereof. Finally, the invention relates to novel polynucleotide sequences and their encoded proteins, which are involved in the biosynthesis of these novel polyketides.

Polyene polyketides, processes for their production and their use as a pharmaceutical

Polyene oxazoles of the following formula wherein Ris selected from H and methyl, are disclosed. Such compounds, and pharmaceutically acceptable salts thereof, may be used in the inhibition of tumor cell growth. The polyene oxazoles and their pharmaceutically acceptable salts may be formulated as pharmaceutical compositions with pharmaceutically acceptable carriers for use in the inhibition of tumor cells. The polyene oxazoles may be obtained from strains of, such as strain 022 having deposit number IDAC 270504-04.

Polyene oxazoles and processes for their preparation

Novel polyene polyketides, their pharmaceutically acceptable salts, prodrugs and derivatives have been found to have antibiotic activity. One method for obtaining the compounds is by cultivation ofATCC&#x2122; 43491 or a mutant or variant such as the strain IDAC-220604-1. Another method for obtaining the compounds is post-biosynthesis chemical modification of the compounds obtained by cultivation. Novel polynucleotide sequences and encoded proteins for the biosynthesis of the polyene polyketides are also presented.

Polyene polyketides and methods of production

This invention provides genes and their encoded proteins, involved in the biosynthesis of farnesyl dibenzodiazepinones, including ECO-04601. The invention relates to expression vectors comprising the genes and to host cell transformed with these vectors. The invention further relates to methods of producing farnesyl dibenzodiazepinone compounds using the genes and proteins of the invention, for example, involving expression of biosynthetic pathway genes in transformed host cells.

Polynucleotides for production of farnesyl dibenzodiazepinones

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

Farnesyl dibenzodiazepinone, and processes for its production

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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Montreal, Canada

Emmanuel Zazopoulos