Methods for increasing the stability of production of compounds in microbial host cells

A non-naturally occurring auxotrophic cyanobacterial cell capable of production of a compound of interest via the expression of at least one exogenous gene wherein the auxotrophic cyanobacterial cell contains an extrachromosomal plasmid comprising the at least one exogenous gene and a gene whose expression complements the auxotrophy of the non-naturally occurring auxotrophic cyanobacterial cell and wherein the at least one exogenous gene and the gene whose expression complements auxotrophy form a polycistronic operon wherein the at least one exogenous gene and the gene whose expression complements auxotrophy are both operably linked to a promoter such that expression of the gene whose expression complements auxotrophy cannot occur without expression of the at least one exogenous gene,

• further wherein the at least one exogenous gene and the gene whose expression complements auxotrophy are linked by an intergenic sequence that is not a promoter,
• further wherein the gene whose expression complements auxotrophy is a nitrogen assimilation gene,
• further wherein cell death occurs if a mutation occurs so that the exogenous gene is not expressed,
• further wherein more of the compound of interest is produced after either 50 days of growth or after a third dilution than if the genes are located on separate operons.