NOVELTY - Altering the phenotype of a cell comprises: (1) mutating a nucleic acid encoding global transcription machinery and, optionally, its promoter, expressing the nucleic acid in a cell to provide an altered cell that includes mutated global transcription machinery, and culturing the altered cell; (2) optionally determining the phenotype of the altered cell; and/or (3) optionally repeating the mutation of the nucleic acid, and preferably determining the phenotype of the nth generation altered cell.    USE - The method is useful in altering the phenotype of a cell to produce cells with improved phenotypes e.g., bioremediation (claimed); identification of genes active in cancer causation (e.g., apoptosis resistance phenotypes); identification of genes active in resistance of bacteria and other prokaryotes to antibiotics and identification of genes active in resistance of pests to pesticides and in industrial production of molecules.    ADVANTAGE - The method of the invention allows exploration of a vastly expanded search space in a high throughput manner by evaluating multiple, simultaneous gene alterations in order to improve complex cellular phenotypes. Further, the cells resulting from introduction of the mutated sigma factors have rapid and marked improvements in phenotypes, such as tolerance of deleterious culture conditions or improved production of metabolites.    DETAILED DESCRIPTION - Altering the phenotype of a cell comprises: (1) mutating a nucleic acid encoding global transcription machinery and, optionally, its promoter, expressing the nucleic acid in a cell to provide an altered cell that includes mutated global transcription machinery, and culturing the altered cell; (2) optionally determining the phenotype of the altered cell; and/or (3) optionally repeating the mutation of the nucleic acid to produce a nth generation altered cell, and preferably determining the phenotype of the nth generation altered cell, where the step of repeating the mutation of the global transcription machinery comprises isolating a nucleic acid encoding the mutated global transcription machinery and optionally, its promoter, from the altered cell, mutating the nucleic acid, and introducing the mutated nucleic acid into another cell.    INDEPENDENT CLAIMS are included for the following:    (1) a cell produced by the method of altering the phenotype of a cell;    (2) a method for altering the production of a metabolite;    (3) a collection comprising different nucleic acid molecule species, where each nucleic acid molecule species encodes global transcription machinery comprising different mutations;    (4) a collection of cells comprising the collection of nucleic acid molecules, each of the cells comprising one or more of the nucleic acid molecules;    (5) a nucleic acid encoding global transcription machinery produced by rounds of mutation, where the rounds of mutation comprise directed evolution comprising mutation by error prone PCR or mutation by gene shuffling;    (6) global transcription machinery encoded by the nucleic acid;    (7) a truncated sigma factor protein comprising (carboxy-terminal) region 4; and    (8) a method for bioremediation of a selected waste product.