Method for stabilizing extra-chromosomal elements in bacteria during cultivation, extra-chromosomal elements, transformed bacteria and a method of producing a desired product in transformed bacteria

摘要

A novel method for stabilization of extra-chromosomal elements in bacteria during cultivation without use of antibiotics in the medium has been developed. The method comprises transformation of a host bacterium having a defect in a chromosomal gene needed for the synthesis or maintenance of the cell envelope with an extra-chromosomal element capable of suppressing the requirement caused by the chromosomal gene defect of the host bacterium. The invention furthermore provides for such transformed bacteria and stabilized extra-chromosomal elements and for a method for producing desirable products by inserting a gene for the desirable product into a stabilized extra-chromosomal element and cultivation of suitable host bacteria containing the stabilized extra-chromosomal element comprising the gene for the desirable product. It was demonstrated that according to the principles of this method, a plasmid including the dal gene of Bacillus subtilis and a gene encoding a desirable product can be maintained in an appropriate dal^-B. subtilis host in conventional media. The method thus allows for improved product yield and quality.