Method of regulating expression of a foreign gene by controlling culture temperature and a process of producing a foreign gene product thereby

DETAILED DESCRIPTION In view of the above-mentioned problems and in quest of establishing more effective means to produce foreign gene products, the present inventors have made several investigations in terms of fermentation technology with regards to the characteristics of E.
coli carrying hybrid plasmids therein.
In the course of the investigations, it was found out that expression of a foreign gene incorporated in a hybrid plasmid in E.
coli was effectively controlled simply by regulating the culture temperature of E.
coli carrying the hybrid plasmid with the foreign gene inserted therein.
Furthermore, the present invention was based on the conclusion that in the production of a foreign gene product by culturing bacteria carrying the hybrid plasmid introduced therein, it is possible to obtain the sufficient bacterial mass containing reduced number of hybrid-plasmid-deleted cells and thereafter to produce the sufficient quantities of the foreign gene product by separating the period of the bacterial growth process from that of the foreign gene expression process to regulate the foreign gene expression by the above regulation of culture temperature in these two periods.
One objective of the present invention is to provide a simple and effective method of controlling expression of a desired foreign gene inserted into a hybrid plasmid in the culture of E.
coli carrying the hybrid plasmid introduced therein.
Another objective of the present invention is to provide an appropriate method of effectively producing a desired foreign gene product in high concentration in the culture, particularly, for producing a foreign gene product on an industrial scale by using E.
coli carrying a hybrid plasmid with an insertion of the foreign gene therein.
A method of regulating expression according to the present invention to achieve the above-mentioned objectives comprises a process of maintaining the temperature of culturing E.
coli at or over 40.
degree.
C.
so as to suppress expression of a desired foreign gene in E