Induction of a Streptomyces Cacaoi Beta-Lactamase Gene Cloned in S. Lividans

The previously cloned class A beta-lactamase gene (bla) of Streptomyces cacaoi was shown to be inducible by beta-lactam compounds in the host organism S. lividans. A regulatory region of 2.75 kb was identified and the nucleotide sequence determined. It contained four open reading frames (ORFs) of which only two were complete and required for induction. ORF1-ORF2 exerted a positive regulatory effect on the expression of bla. Inactivation of ORF1 or of ORF2 resulted not only in the loss of induction, but also in a 30- to 60-fold decrease in the basal (non-induced) level of beta-lactamase production. ORF1 codes for a DNA-binding protein related to the AmpR repressor/activator, which controls the expression of ampC (class C beta-lactamase) genes in several Enterobacteria