摘要:
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.
摘要:
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.
摘要:
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.
摘要:
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.
摘要:
Genes and proteins involved in the biosynthesis of lipopeptides by microorganisms, in particular the nucleic acids forming the biosynthetic locus for the A54145 lipopeptide from Streptomyces fradiae and the A54145-like lipopeptide from Streptomyces refuineus. 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.
摘要:
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 as Actinoplanes sp. The isolated gene sequence serves as a substrate for bioengineering of antibiotic structures.
摘要:
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.
摘要:
Polyene oxazoles of the following formula wherein R3 is 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 Streptomyces sparsogenes, such as strain 022 having deposit number IDAC 270504-04.
摘要:
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.
摘要:
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.