Abstract: The present invention is directed to methods and compositions for use of homologous recombination for directed evolution, gene reassembly, and directed mutagenesis. One aspect of the present invention relates to methods for use of bacterial conjugative transfer and homologous recombination for directed evolution, gene reassembly, and directed mutagenesis. Another aspect of the present invention relates to compositions for use in or produced by the methods of the present invention, including libraries, archives and databases.

Abstract: The present invention is directed to methods and compositions for use of homologous recombination for directed evolution, gene reassembly, and directed mutagenesis. One aspect of the present invention relates to methods for use of bacterial conjugative transfer and homologous recombination for directed evolution, gene reassembly, and directed mutagenesis. Another aspect of the present invention relates to compositions for use in or produced by the methods of the present invention, including libraries, archives and databases.

Abstract: The present invention provides libraries of tag dominant-negative elements (TDNE) and methods the identification specific TDNEs that act as dominant-negative elements on a target protein of interest. The present invention further relates to the use of such TDNEs and dominant-negative elements for the identification of protein-protein interactions, and the determination of a target protein's biological activity and function. Furthermore, the present invention relates to the development of means, including small molecule compounds, for disrupting the target protein's biological function and activity.

Abstract: The present invention is directed to methods and compositions for use of homologous recombination for directed evolution, gene reassembly, and directed mutagenesis. One aspect of the present invention relates to methods for use of bacterial conjugative transfer and homologous recombination for directed evolution, gene reassembly, and directed mutagenesis. Another aspect of the present invention relates to compositions for use in or produced by the methods of the present invention, including libraries, archives and databases.

Abstract: The present invention relates to methods and compositions for the identification and modulation of protein-protein interactions. Specifically, the invention relates to methods and compositions for efficient, sensitive, high-throughput CadC-based screens for the identification of peptides involved in protein-protein interactions, including, but not limited to, peptides comprising amino acid sequences involved in receptor dimerization. The invention further relates to methods and compositions for efficient, sensitive, high-throughput CadC-based screens for compounds which modulate protein-protein interactions, such as, for example, modulation of interactions between protein sequences involved in receptor interactions, e.g., dimerization.

Abstract: The present invention relates to methods and compositions for the modulation of bacterial topoisomerase enzymes within bacterial cells. More specifically, the present invention relates to bacterial assays wherein the levels of bacterial topoisomerase enzymes or the levels of target sites within the enzymes are varied within bacterial test strains in order to screen for compounds that target, i.e., interact with the topoisomerase enzymes, causing DNA damage and hence, bacterial growth inhibition and/or cell death. The present methods and compositions are useful for the identification and characterization of novel therapeutic antibacterial compounds.

Abstract: The present invention relates to:(1) a fusion protein having a dimerizing domain with or without a ligand-binding region and toxR DNA-binding and hydrophobic transmembrane regions;(2) host cells comprising the fusion protein and a nucleic acid molecule having a reporter gene operatively linked to the ctx operon, wherein dimerization (ligand-dependent or -independent) is signaled by expression of the reporter gene;(3) a nucleic acid molecule coding for the fusion protein;(4) an expression vector comprising a coding region for the fusion protein;(5) a process for detecting dimer formation (ligand dependent or ligand independent) of the fusion protein, which comprises treating a culture of the host cells with a ligand, ligand mimetic, or dimerization inhibitor, and screening for expression of the reporter gene.The present invention can be used to generate a signal from a variety of ligand-binding domains, allowing ligand binding to be indicated by a simple colorimeteric test or antibiotic resistance.

Abstract: Expression vectors for human topoisomerase I and a method for detecting poisons of human topoisomerase I. The vector preferably contains a promoter, DNA coding for human topoisomerase I, DNA coding for a selectable marker, an origin of replication, and lac I.sup.q DNA which encodes a repressor for the promoter.

Abstract: Hayumicin compounds, obtainable by cultivation of a strain of Actinomadura sp. designated ATCC 55432, and analogs of these compounds. The novel compounds have antitumor as well as antibiotic, particularly antibacterial, activity.

Abstract: The present invention relates to:(1) a fusion protein having a dimerizing domain with or without a ligand-binding region and toxR DNA-binding and hydrophobic transmembrane regions;(2) host cells comprising the fusion protein and a nucleic acid molecule having a reporter gene operatively linked to the ctx operon, wherein dimerization (ligand-dependent or -independent) is signaled by expression of the reporter gene;(3) a nucleic acid molecule coding for the fusion protein;(4) an expression vector comprising a coding region for the fusion protein;(5) a process for detecting dimer formation (ligand dependent or ligand independent) of the fusion protein, which comprises treating a culture of the host cells with a ligand, ligand mimetic, or dimerization inhibitor, and screening for expression of the reporter gene.The present invention can be used to generate a signal from a variety of ligand-binding domains, allowing ligand binding to be indicated by a simple colorimetric test or antibiotic resistance.