Abstract: Disclosed is a synthetic gene cluster for producing gadusol derivatives, expression vectors and host cells containing the same, methods of producing gadusol derivatives, and compositions thereof. In an example, the synthetic gene cluster includes a valA nucleotide sequence capable of expressing ValA protein; a nucleotide sequence capable of expressing methyltransferase/oxidoreductase (MT-Ox) protein; a mysC nucleotide sequence capable of expressing a MysC protein; and a mysD nucleotide sequence capable of expressing a MysD protein. In this way, gadusol derivatives can be produced in amounts sufficient for use in a variety of applications.

Abstract: Disclosed is a synthetic gene cluster for producing gadusol derivatives, expression vectors and host cells containing the same, methods of producing gadusol derivatives, and compositions thereof. In an example, the synthetic gene cluster includes a valA nucleotide sequence capable of expressing ValA protein; a nucleotide sequence capable of expressing methyltransferase/oxidoreductase (MT-Ox) protein; a mysC nucleotide sequence capable of expressing a MysC protein; and a mysD nucleotide sequence capable of expressing a MysD protein. In this way, gadusol derivatives can be produced in amounts sufficient for use in a variety of applications.

Abstract: The present disclosure relates to engineered microorganisms capable of producing gadusol. The engineered microorganisms contain a nucleotide sequence encoding 2-epi-5-valione synthase (EEVS) and a nucleotide sequence encoding methyltransferase-oxidoreductase (MT-Ox). Methods of using the engineered microorganisms to produce gadusol, including the culturing of such microorganisms, are also described.

Abstract: Disclosed is a synthetic gene cluster for producing gadusol derivatives, expression vectors and host cells containing the same, methods of producing gadusol derivatives, and compositions thereof. In an example, the synthetic gene cluster includes a valA nucleotide sequence capable of expressing ValA protein; a nucleotide sequence capable of expressing methyltransferase/oxidoreductase (MT-Ox) protein; a mysC nucleotide sequence capable of expressing a MysC protein; and a mysD nucleotide sequence capable of expressing a MysD protein. In this way, gadusol derivatives can be produced in amounts sufficient for use in a variety of applications.

Abstract: The present disclosure relates to engineered microorganisms capable of producing gadusol. The engineered microorganisms contain a nucleotide sequence encoding 2-epi-5-valione synthase (EEVS) and a nucleotide sequence encoding methyltransferase-oxidoreductase (MT-Ox). Methods of using the engineered microorganisms to produce gadusol, including the culturing of such microorganisms, are also described.

Abstract: This disclosure describes the molecular cloning of a pactamycin biosynthetic gene cluster from Streptomyces pactum ATCC 27456, characterization of individual genes in the gene cluster and the proteins encoded thereby as well as uses thereof. The pactamycin gene cluster is located within an 86.35 kilobases genetic locus and includes 53 open reading frames, 26 of which are considered to be the core cluster directly involved in the biosynthesis of pactamycin. The present disclosure also relates to the use of the pactamycin biosynthetic genes located within the identified gene cluster for drug design and development purposes, including the development of pactamycin analogs that are more efficacious and less toxic. Also provided are drugs and antibiotics so produced, as well as methods of their use.

Abstract: This disclosure describes the molecular cloning of a pactamycin biosynthetic gene cluster from Streptomyces pactum ATCC 27456, characterization of individual genes in the gene cluster and the proteins encoded thereby as well as uses thereof. The pactamycin gene cluster is located within an 86.35 kilobases genetic locus and includes 53 open reading frames, 26 of which are considered to be the core cluster directly involved in the biosynthesis of pactamycin. The present disclosure also relates to the use of the pactamycin biosynthetic genes located within the identified gene cluster for drug design and development purposes, including the development of pactamycin analogs that are more efficacious and less toxic. Also provided are drugs and antibiotics so produced, as well as methods of their use.

Abstract: This disclosure describes the molecular cloning of a pactamycin biosynthetic gene cluster from Streptomyces pactum ATCC 27456, characterization of individual genes in the gene cluster and the proteins encoded thereby as well as uses thereof. The pactamycin gene cluster is located within an 86.35 kilobases genetic locus and includes 53 open reading frames, 26 of which are considered to be the core cluster directly involved in the biosynthesis of pactamycin. The present disclosure also relates to the use of the pactamycin biosynthetic genes located within the identified gene cluster for drug design and development purposes, including the development of pactamycin analogs that are more efficacious and less toxic. Also provided are drugs and antibiotics so produced, as well as methods of their use.

Abstract: Disclosed are pactamycin analogs, pharmaceutical compositions including the analogs, and methods of using the analogs, such as to inhibit tumor growth or a pathogenic infection such as a bacterial or parasitic infection. The pactamycin analogs have a general formula where R1 is H, lower aliphatic, amide, acyl, or aminoacyl; R2 is —C(O)NR8R9 where R8 and R9 independently are hydrogen or lower aliphatic, or R1 and R2 together form a cyclic structure; R3 and R4 independently are hydrogen, hydroxyl, or lower aliphatic, or R2 and R3 together form a cyclic structure; R5 is hydrogen or acyl; R6 and R7 independently are hydrogen, hydroxyl, halogen, lower aliphatic, or amino.

Abstract: This disclosure relates to validamycin A biosynthesis and in particular, to methods of producing validamycin A analogs and uses thereof. In a particular example, a method for making a validamycin A analog includes transforming a host cell with one or more recombinant DNA vectors to produce a valN-inactivated mutant; and culturing the valN-inactivated mutant in a culture medium to produce a validamycin A analog, such as 1,1?-bis-valienamine and validienamycin, and their conversion to valienamine. The present disclosure further relates to compositions including such compounds as well as methods of using the compositions, such as for antifungal agents.

Abstract: This disclosure describes the molecular cloning of a pactamycin biosynthetic gene cluster from Streptomyces pactum ATCC 27456, characterization of individual genes in the gene cluster and the proteins encoded thereby as well as uses thereof. The pactamycin gene cluster is located within an 86.35 kilobases genetic locus and includes 53 open reading frames, 26 of which are considered to be the core cluster directly involved in the biosynthesis of pactamycin.

Abstract: This disclosure relates to validamycin A biosynthesis and in particular, to methods of producing validamycin A analogs and uses thereof. In a particular example, a method for making a validamycin A analog includes transforming a host cell with one or more recombinant DNA vectors to produce a valN-inactivated mutant; and culturing the valN-inactivated mutant in a culture medium to produce a validamycin A analog, such as 1,1?-bis-valienamine and validienamycin, and their conversion to valienamine. The present disclosure further relates to compositions including such compounds as well as methods of using the compositions, such as for antifungal agents.