One of the major obstacles to the use of recombinant DNA-containing organisms for the large-scale production of proteins in commercial processes is the cells genetic instability. Genetic instabilities manifest themselves in the spontaneous formation of non-productive microbial strains which lower overall yields and preempt the use of long term continuous culture processing strategies. Host-vector systems containing obligatory plasmids will be constructed. In each system, the single-stranded binding protein gene will be removed from the genome of E. coli but provided for the cell by including it on a plasmid. Loss of the plasmid should then be fatal to the host cell, and instability caused by plasmid segregation in reactor systems should be eliminated. Production of B-lactmase will be used as a measure of protein production culture. A convenient polylinker, a high production plasmid containing a strong promotor, will be constructed to facilityate future cloning of industrial interest.
