An engineered microbial organism cell comprising: (a) an endogenous gene or genomic region to be targeted that encodes a functional protein having a first detectable phenotype, and a heterologous polynucleotide sequence encoding a phenotype coding sequence operably linked to a promoter that (i) encodes a second functional protein having a second detectable phenotype, or (ii) comprises an engineered disruption in a sequence encoding the second protein that prevents expression of the second detectable phenotype for gene alteration or one or more heterologous polynucleotide sequences comprising: a first phenotype coding sequence operably linked to a promoter, wherein the first phenotype coding sequence either (i) encodes a first functional protein having a first detectable phenotype, or (ii) comprises an engineered disruption in a sequence encoding protein that prevents expression of the first detectable phenotype; and a second phenotype coding sequence operably linked to a promoter, wherein the second phenotype coding sequence either (i) encodes a second functional protein having a second detectable phenotype, or (ii) comprises an engineered disruption in a sequence encoding the second protein that prevents expression of the second detectable phenotype; wherein each of the first and the second detectable phenotypes is a detectable color, fluorescence, scent, enzymatic activity, antibiotic resistance, morphology or lethality; (b) a heterologous polynucleotide sequence comprising a promoter operably linked to a polynucleotide encoding a Cas nuclease and a heterologous polynucleotide sequence comprising a guide RNA (gRNA) that targets the first phenotype coding sequence, a gRNA that targets the second phenotype coding sequence; and a heterologous polynucleotide sequence comprising a promoter operably linked to a polynucleotide encoding lambda red. (a) an endogenous gene or genomic region to be targeted that encodes a functional protein having a first detectable phenotype, and a heterologous polynucleotide sequence encoding a phenotype coding sequence operably linked to a promoter that (i) encodes a second functional protein having a second detectable phenotype, or (ii) comprises an engineered disruption in a sequence encoding the second protein that prevents expression of the second detectable phenotype for gene alteration or one or more heterologous polynucleotide sequences comprising: a first phenotype coding sequence operably linked to a promoter, wherein the first phenotype coding sequence either (i) encodes a first functional protein having a first detectable phenotype, or (ii) comprises an engineered disruption in a sequence encoding protein that prevents expression of the first detectable phenotype; and a second phenotype coding sequence operably linked to a promoter, wherein the second phenotype coding sequence either (i) encodes a second functional protein having a second detectable phenotype, or (ii) comprises an engineered disruption in a sequence encoding the second protein that prevents expression of the second detectable phenotype; wherein each of the first and the second detectable phenotypes is a detectable color, fluorescence, scent, enzymatic activity, antibiotic resistance, morphology or lethality; a first phenotype coding sequence operably linked to a promoter, wherein the first phenotype coding sequence either (i) encodes a first functional protein having a first detectable phenotype, or (ii) comprises an engineered disruption in a sequence encoding protein that prevents expression of the first detectable phenotype; and a second phenotype coding sequence operably linked to a promoter, wherein the second phenotype coding sequence either (i) encodes a second functional protein having a second detectable phenotype, or (ii) comprises an engineered disruption in a sequence encoding the second protein that prevents expression of the second detectable phenotype; wherein each of the first and the second detectable phenotypes is a detectable color, fluorescence, scent, enzymatic activity, antibiotic resistance, morphology or lethality; (b) a heterologous polynucleotide sequence comprising a promoter operably linked to a polynucleotide encoding a Cas nuclease and a heterologous polynucleotide sequence comprising a guide RNA (gRNA) that targets the first phenotype coding sequence, a gRNA that targets the second phenotype coding sequence; and a heterologous polynucleotide sequence comprising a promoter operably linked to a polynucleotide encoding lambda red.