Regulation of β-Galactosidase Synthesis in Escherichia coli by Cyclic Adenosine 3′,5′-Monophosphate

Abstract Cyclic adenosine 3',5'-monophosphate (cyclic AMP) increases the differential rate of synthesis of β-galactosidase in Escherichia coli made permeable by treatment with tris(hydroxymethyl)aminomethane and ethylenediamintetraacetic acid. In normal, growing cells, cyclic AMP overcomes the transient repression of β-galactosidase by glucose. A half-maximal effect of cyclic AMP occurs at about 7 x 10-5 m. Cyclic AMP overcomes the transient repression of β-galactosidase synthesis in two regulatory mutants which produce β-galactosidase constitutively, 3300 (i-) and Oc67. Cyclic AMP also acts in cells which are deficient in the lac permease. Cyclic AMP overcomes the transient repression of β-galactosidase synthesis produced by α-methylglucoside in strain C600 which has normal regulatory genes. In mutant LA-12G, which is resistant to permanent repression, cyclic AMP also overcomes transient glucose repression. In cells treated with chloramphenicol, isopropylthio-β-d-galactopyranoside promotes the accumulation of β-galactosidase-specific messenger RNA, glucose prevents its accumulation, and cyclic AMP overcomes this repression by glucose. Cyclic AMP also overcomes the glucose repression of mRNA production in a threonine-requiring mutant during threonine starvation. Cyclic AMP fails to stimulate β-galactosidase production in cells in which mRNA synthesis has been arrested by inducer removal or proflavine addition. Thus, cyclic AMP appears to participate in the regulation of β-galactosidase mRNA synthesis at the gene level.