Two-stage fermentation with bacteriophage lambda as an expression vector in Escherachia coli

The potential of bacteriophage lambda as an expression vector for a large scale production of cloned-gene proteins was evaluated in batch and continuous bioreactors using a temperature-sensitive mutant in the cl gene, which allows a simple manipulation of temperature as a means to control the phage in the lysogenic or lytic state. A temperature switch from 32 degrees C (or below) to 38 degrees C (or above) forces the phage to go from the lysogenic state to the lytic state. Temperature cycling and a two-reactor system were used for continuous cultures. For the latter the first reactor is maintained in the lysogenic state at a lower temperature to stably maintain the foreign DNA in the host cell, while the second reactor is maintained in the lytic state to force replication of the cloned-gene and overproduction of its products. The results are promising but suggest a greater potential for a mutant which lacks the Q gene which is responsible for host cell lysis and packaging of phage particles.