Abstract: Recombinant host cells that produce rapamycin analogues are constructed by deleting or modifying rapamycin biosynthetic gene cluster genes and are useful in the production of compounds used as antifungals, anticancers, immunosuppressants, and neurotrophins.

Abstract: Materials and methods to produce modified polyketides are disclosed. The biosynthesis, transfer and regulator genes for various sugars to effectuate polyketide modification are disclosed.

Abstract: Isolated and purified Staphylococcus thioredoxin reductases (TrxB) are provided. Polynucleotides encoding the TrxBs, vectors and host cells containing such polynucleotides are also provided. In addition, antibodies reactive with the TrxBs are provided, as are methods of isolating the TrxBs, as well as methods for producing recombinant TrxBs, using TrxBs for screening compounds for TrxB-modulating activity, and detecting Staphylococcus in a test sample.

Abstract: Isolated and purified Staphylococcus thioredoxin reductases (TrxB) are provided. Polynucleotides encoding the TrxBs, vectors and host cells containing such polynucleotides are also provided. In addition, antibodies reactive with the TrxBs are provided, as are methods of isolating the TrxBs, as well as methods for producing recombinant TrxBs, using TrxBs for screening compounds for TrxB-modulating activity, and detecting Staphylococcus in a test sample.

Abstract: Domains of chalcomycin polyketide synthases and modification enzymes and polynucleotides encoding them are provided. Methods to prepare chalcomycin in pharmaceutically useful quantities are described, as are methods to prepare chalcomycin analogs and other polyketides using the polynucleotides encoding chalcomycin polyketide synthase domains or modifying enzymes.

Abstract: Recombinant host cells that produce rapamycin analogues are constructed by deleting or modifying rapamycin biosynthetic gene cluster genes and are useful in the production of compounds used as antifungals, anticancers, immunosuppressants, and neurotrophins.

Abstract: Recombinant host cells that comprise recombinant DNA expression vectors that drive expression of a product and a precursor for biosynthesis of that product can be used to produce useful products such as polyketides in host cells that do not naturally produce the product or produce the product at low levels due to the absence of the precursor or the presence of the precursor in rate limiting amounts.

Abstract: The present invention provides bioconversion methods for making epothilone analogs. These analogs differ from the starting material by the addition of one or more hydroxyl groups or by the addition of an epoxide. These compounds, in turn, can be further modified by chemical synthesis.

Abstract: Recombinant host cells that comprise recombinant DNA expression vectors that drive expression of a product and a precursor for biosynthesis of that product can be used to produce useful products such as polyketides in host cells that do not naturally produce the product or produce the product at low levels due to the absence of the precursor or the presence of the precursor in rate limiting amounts.

Abstract: Compounds of the invention include 14-mehtyl epothilone derivatives. More generally, preferred compounds of the invention are those that can be produced by altering the epothilone PKS genes as described herein and optionally by action of epothilone modification enzymes and/or by chemically modifying the resulting epothilones produces when those genes are expressed.

Abstract: Recombinant host cells of the suborder Cystobacterineae containing recombinant expression vectors that encode heterologous PKS genes can produce polyketides synthesized by the PKS enzymes encoded on those vectors at high levels.

Abstract: Recombinant Myxococcus host cells can be used to produce polyketides, including epothilone and epothilone analogs that can be purified from the fermentation broth and crystallized.

Abstract: The invention provides novel erythromycin derivatives in which methyl groups on the macrolactone ring have been substituted with —H, -Et, and/or —OH. The invention also provides reagents such as isolated polynucleotides, vectors comprising the polynucleotides and host cells transformed with the vectors for making the novel compounds. Methods for making the compounds utilizing genetic engineering techniques are also disclosed.

Abstract: The present invention provides novel sixteen-membered macrolide compounds that are useful as anti-infective agents or as intermediates thereto. The present invention also provides methods for the preparation of these compounds, and methods and formulations for their use. In one aspect of the present invention, sixteen-membered macrolide possessing a side chain Z are provided where Z is aliphatic, aryl, alkylaryl, halide, ═NOR3, ═NNHR3, or —W—R3 where W is O, S, NC(═O)R4, NC(═O)OR4, NC(═O)NHR4 or NR4 where R3 and R4 are each independently hydrogen, aliphatic, aryl or alkylaryl. In another aspect of the present invention, bicyclic compounds are provided where one of the cyclic-components is a sixteen-membered macrolide and the other is a cyclic moiety whose cyclic structure is formed by between 3 and 10 atoms. In another aspect of the present invention, sixteen-membered macrolide compounds that bind to the domain II region of the 23S RNA are provided.

Abstract: The present invention provides novel sixteen-membered macrolide compounds that are useful as anti-infective agents or as intermediates thereto. The present invention also provides methods for the preparation of these compounds, and methods and formulations for their use. In one aspect of the present invention, sixteen-membered macrolide possessing a side chain Z are provided where Z is aliphatic, aryl, alkylaryl, halide, ═NOR3, ═NNHR3, or —W—R3 where W is O, S, NC(═O)R4, NC(═O)OR4, NC(═O)NHR4 or NR4 where R3 and R4 are each independently hydrogen, aliphatic, aryl or alkylaryl. In another aspect of the present invention, bicyclic compounds are provided where one of the cyclic-components is a sixteen-membered macrolide and the other is a cyclic moiety whose cyclic structure is formed by between 3 and 10 atoms. In another aspect of the present invention, sixteen-membered macrolide compounds that bind to the domain II region of the 23S RNA are provided.

Abstract: Recombinant Myxococcus host cell containing recombinant expression vectors containing epothilone polyketide synthase genes can produce epothilones C and D.

Abstract: Recombinant nucleic acids that encode all or a portion of the epothilone polyketide synthase (PKS) are used to express recombinant PKS genes in host cells for the production of epothilones, epothilone derivatives, and polyketides that are useful as cancer chemotherapeutics, fungicides, and immunosuppressants.

Abstract: The invention provides novel erythromycin derivatives in which methyl groups on the macrolactone ring have been substituted with —H, -Et, and/or —OH. The invention also provides reagents such as isolated polynucleotides, vectors comprising the polynucleotides and host cells transformed with the vectors for making the novel compounds. Methods for making the compounds utilizing genetic engineering techniques are also disclosed.

Abstract: An isolated and purified Coenzyme A disulfide reductase (CoADR) is provided. Oligonucleotides encoding the CoADR, vectors and host cells containing such oligonucleotides are also provided. In addition, antibodies reactive with the CoADR are provided, as are methods of isolating the CoADR, producing recombinant CoADR, using CoADR for screening compounds for CoADR-modulating activity, and detecting organisms which produce CoADR a test sample. Methods for identifying a gene encoding a CoADR are also provided.

Abstract: The invention provides novel erythromycin derivatives in which methyl groups on the macrolactone ring have been substituted with --H, -Et, and/or --OH and the ethyl side-chain has been substituted with hydroxymethyl or dihydroxycyclohexylmethyl side-chains. The invention also provides reagents such as isolated polynucleotides, vectors comprising the polynucleotides and host cells transformed with the vectors for making the novel compounds. Methods for making the compounds utilizing genetic engineering techniques are also disclosed.