Abstract: The invention relates to a method and system for identifying a secondary metabolite synthesized by a target gene cluster within a microorganism. A putative or confirmed function is attributed to a gene within the gene cluster, and an extract from the microorganism is obtained which is suspected to contain the secondary metabolite synthesized by the gene cluster. The extract is then assessed for chemical, physical or biological properties, and the metabolite is identified and optionally isolated. Further, the invention provides a knowledge repository in which gene cluster information is linked to secondary metabolite production data. The invention further relates to a graphical user interface for accessing the knowledge repository, and a memory for storing data, having a data structure that is stored in the memory.

Abstract: 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 Streptomyces aizunensis; another method involves expression of biosynthetic pathway genes in transformed host cells. The present invention further relates to the novel strains of Streptomyces aizunensis used 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.

Abstract: Genes and proteins involved in the biosynthesis of benzodiazepines by microorganisms, including the genes and proteins forming the biosynthetic loci for the benzodiazepine anthramycin from Streptomyces refuineus subsp. thermotolerans. 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.

Abstract: Described are methods and systems for identifying a secondary metabolite synthesized by a target gene cluster within a microorganism. A putative or confirmed function is attributed to a gene within the gene cluster, and an extract from the microorganism is obtained which is suspected to contain the secondary metabolite synthesized by the gene cluster. The extract is then assessed for chemical, physical or biological properties, and the metabolite is identified and optionally isolated. Further, the invention provides a knowledge repository in which gene cluster information is linked to secondary metabolite production data. The invention further relates to a graphical user interface for accessing the knowledge repository, and a memory for storing data, having a data structure that is stored in the memory.

Abstract: 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.

Abstract: This invention relates to methods of inhibiting growth and/or proliferation of a neoplastic cell, and methods of treating neoplasms using the farnesylated dibenzodiazepinone compound of Formula I.

Abstract: 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 as Actinoplanes sp. The isolated gene sequences serve as substrates for bioengineering of antibiotic structures.

Abstract: This invention related to methods of inhibiting the growth of bacterial cells and methods of treating bacterial infections in mammals using a novel polyene polyketide.

Abstract: 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 Streptomyces aizunensis; another method involves expression of biosynthetic pathway genes in transformed host cells. The present invention further relates to the novel strains of Streptomyces aizunensis used 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.

Abstract: 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 of Amycolatopsis orientalis ATCC™ 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.

Abstract: 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.

Abstract: 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.

Abstract: This invention relates to methods of inhibiting growth of a cancer cell and methods of treating cancer using a novel farnesylated dibenzodiazepinone.

Abstract: 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 of Micromonospora sp., 046-ECO11; another method involves expression of biosynthetic pathway genes in transformed host cells. The present invention further relates to Micromonospora sp. 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.

Abstract: Novel polyene oxazole compounds of Formula I: are useful as cytotoxic agents. The polyene oxazoles may be made by fermentation of Streptomyces sparsogenes and optional post-biosynthesis chemical modification thereof.

Abstract: This invention relates to a novel class of linear polyene polyketides, their pharmaceutically acceptable salts and derivatives, and to methods for their production. The compounds may be obtained by cultivation of Streptomyces melanosporafaciens species and isolation of the polyene polyketide, followed by optional chemical production of the isolated polyene polyketide. The compounds may also be produced by other known bacteria. The invention further includes the use of these compounds as inhibitors of fungal cell growth and inhibitors of cancer cell growth. Finally, the invention encompasses pharmaceutical compositions comprising these novel polyketide compounds, or their pharmaceutically acceptable salts or derivatives thereof.