TECHNOLOGY FOCUS - BIOTECHNOLOGY - Preferred Method: 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. The cell is a prokaryotic cell, preferably a bacterial cell or an archaeal cell. The global transcription machinery is a sigma factor or an anti-sigma factor, where a nucleic acid encoding the sigma factor is a rpoD (sigma70) gene, a rpoF (sigma28) gene, a rpoS (sigma38) gene, a rpoH (sigma32) gene, a rpoN (sigma54) gene, a rpoE (sigma24) gene or a fecI (sigma19) gene. The sigma factor or anti-sigma factor is expressed from an expression vector. The cell is a eukaryotic cell, preferably a yeast cell, a mammalian cell, a plant cell, an insect cell, a stem cell, or a fungus cell. The eukaryotic cell is contained in a multicellular organism. The nucleic acid is expressed in the cell from a tissue-specific promoter, a cell-specific promoter, or an organelle-specific promoter. The nucleic acid is a nucleic acid of an organelle of the eukaryotic cell. The organelle is a mitochondrion or a chloroplast. The global transcription machinery binds to an RNA polymerase I, II or III, or its promoter. The global transcription machinery is a nucleic acid methyltransferase, a histone methyltransferase, a histone acetylase or a histone deacetylase, TFIID or its subunit, comprising TATA-binding protein (TBP) or a TBP-associated factor (TAF). The nucleic acid encoding the global transcription machinery is a GAL11 gene, a SIN4 gene, a RGR1 gene, a HRS1 gene, a PAF1 gene, a MED2 gene, a SNF6 gene, a SNF2 gene, or a SW11 gene. The global transcription machinery is expressed from an expression vector. The nucleic acid is part of an expression vector and/or is a member of a collection of nucleic acids. The method further comprises introducing the collection into the cell. The step of expressing the nucleic acid comprises integrating the nucleic acid into the genome or replacing a nucleic acid that encodes the endogenous global transcription machinery. The mutation of the nucleic acid comprises directed evolution of the nucleic acid, preferably mutation by error prone PCR or mutation by gene shuffling. The mutation of the nucleic acid comprises synthesizing the nucleic acid with one or more mutations. The nucleic acid mutations is/are one or more point mutations and/or one or more truncations or deletions. A promoter binding region of the global transcription machinery is not disrupted or removed by the one or more truncations or detections. The mutated global transcription machinery exhibits increased or decreased transcription of genes relative to the unmutated global transcription machinery. The mutated global transcription machinery exhibits increased or decreased repression of gene transcription relative to the unmutated global transcription machinery. The method further comprises selecting the altered cell for a predetermined phenotype. The step of selecting comprises culturing the altered cell under selective conditions or high-throughput assays of individual cells for the phenotype, where the cell is contained in a multicellular organism. The phenotype is increased tolerance of deleterious culture conditions, preferably solvent tolerance or hazardous waste tolerance, where the solvent is ethanol, hexane or cyclohexane; tolerance of industrial media; tolerance of high sugar concentration; tolerance of high salt concentration; tolerance of high temperatures; tolerance of extreme pH; tolerance of surfactants; tolerance of deleterious conditions; increased metabolite production, preferably lycopene, polyhydroxybutyrate (PHE), or a therapeutic protein, such as an antibody or an antibody fragment; tolerance of a toxic substrate, metabolic intermediate or product, preferably an organic solvent, acetate or para -hydroxybenzoic acid (pHEA), or an overexpressed protein; antibiotic resistance; increased resistance to apoptosis; one or more growth characteristics; generation time; resistance to one or more pests or diseases; production of fruit or other parts of a plant; one or more developmental changes; one or more lifespan alterations; gain or loss of function; and/or increased robustness. The cell used in the method is optimized for the phenotype prior to mutating the global transcription machinery. The method further comprises identifying the changes in gene expression in the altered cell. The changes in gene expression are determined using a nucleic acid microarray. The method comprises altering the expression of one or more gene products in a first cell that are identified by detecting changes in gene expression in a second cell, where the changes in gene expression in the second cell are produced by mutating global transcription machinery of the second cell. Altering the expression of the one or more gene products in the first cell comprises increasing expression of one or more gene products that were increased in the second cell, optionally where the expression of the one or more gene products is increased by introducing into the first cell one or more expression vectors that express the one or more gene products and/or by increasing the transcription of one or more endogenous genes that encode the one or more gene products, preferably where increasing the transcription of the one or more endogenous genes comprises mutating a transcriptional control sequence of the one or more genes. Altering the expression of the one or more gene products in the first cell comprises decreasing expression of one or more gene products that were decreased in the altered cell. The expression of the one or more gene products is decreased by introducing into the first cell nucleic acid molecules that reduce the expression of the one or more gene products. The nucleic acid molecules are, or express, siRNA molecules, or where the expression of the one or more gene products is decreased by mutating one or more genes that encode the one or more gene products or a transcriptional control sequence of the one or more genes. The changes in gene expression in the second cell are determined using a nucleic acid microarray. The changes in gene expression in the second cell are used to construct a model of a gene or protein network. The model is used to select which of the one or more gene products in the network to alter. The global transcription machinery comprises more than one nucleic acid and/or polypeptide or is encoded by more than one nucleic acid. Altering the production of a metabolite comprises mutating global transcription machinery of a cell that produces a selected metabolite to produce an altered cell, and isolating altered cells that produce increased or decreased amounts of the selected metabolite. The method comprises culturing the isolated cells, and recovering the metabolite from the cells or the cell culture. The metabolite is lycopene; polyhydroxybutyrate (PHE); or a therapeutic protein, preferably a recombinant protein, an antibody or an antibody fragment. The cells are prokaryotic cells, preferably bacterial cells or archaeal cells; or eukaryotic cells, preferably yeast cells, mammalian cells, plant cells, insect cells, stem cells or fungus cells. The global transcription machinery is encoded by nucleic acid of an organelle of the eukaryotic cell, preferably a mitochondrion or a chloroplast. The nucleic acid molecule species are contained in expression vectors, where the nucleic acid is expressed from a tissue-specific promoter, a cell-specific promoter, or an organelle specific promoter, and/or where the expression vectors contain different nucleic acid molecule species, where each nucleic acid molecule species encodes different global transcription machinery. The global transcription machinery is mutated by directed evolution, preferably where the directed evolution is performed using error prone PCR or gene shuffling. The mutations in the global transcription machinery are one or more point mutations and/or one or more truncations or deletions, preferably where the truncation does not include the promoter binding region of the global transcription machinery. The global transcription machinery of a cell is mutated. The method for bioremediation of a selected waste product comprises:(1) mutating global transcription machinery of a cell to produce an altered cell;(2) isolating altered cells that metabolize an increased amount of the selected waste product relative to unaltered cells;(3) culturing the isolated cells; and(4) exposing the altered cells to the selected waste product, thereby providing bioremediation of the selected waste product.Preferred Cells: The cells are prokaryotic cells, preferably bacterial cells or archaeal cells, or eukaryotic cells, preferably yeast cells, mammalian cells, plant cells, insect cells, stem cells or fungus cells. The nucleic acid molecules are integrated into the genome of the cells or replace nucleic acids that encode transcription machinery. Preferred Nucleic Acid: The nucleic acid encodes different global transcription machinery species or different versions of the same type of global transcription machinery species. EXAMPLE - No suitable example given.