REGULATION 127 



few facts which throw hght upon the mechanism of protein synthesis and 

 upon its control will be considered here. 



1 . Induced Sy?ithesis of Enzymes in Micro-organisms 



Enzymic adaptation refers to the adjustment of a specific enzyme 

 activity caused by a change of the medium under such conditions that 

 selection of mutants can be excluded. In several cases, it has been clearly 

 established that the adaptive increase of certain enzyme activities in micro- 

 organisms corresponds to the complete de novo synthesis of the enzyme 

 proteins (e.g. Cohn and Toriani, 1953). For instance, E. coli was grown in 

 a medium containing radioactive protein precursors so that every protein 

 present in the bacteria was strongly labelled. The bacteria were then trans- 

 ferred into a non-labelled medium and induced by a galactoside to make 

 ^-galactosidase. The enzyme was isolated in a state of great purity, and its 

 radioactivity was measured. Practically no label was found in the enzyme ; 

 ^-galactosidase had been synthesized completely from non-radioactive pre- 

 cursors, it did not pre-exist in the cell in any form before the addition of the 

 inducer galactoside. The inducer therefore caused the complete synthesis 

 of the enzyme from amino acids (Rotman and Spiegelman, 1954; Hogness 

 et al., 1955). The usual genetic control of enzyme synthesis remains, how- 

 ever, for certain mutant strains of E. coli are unable to make jS-galactosidase 

 even in the presence of galactosides (Lederberg, 1951); these strains result 

 from mutations which are all located within a narrow region of the genome, 

 called the z locus (Pardee et al., 1959; Monod, 1960). Transfer of a small 

 piece of genome containing the z locus to a Shigella confers to this bacter- 

 ium the capacity of making a galactosidase which is identical to the coli 

 enzyme (Cohn et al., 1960). The z region of the genome must be the locus 

 which specifically controls the primary structure of the enzyme. 



What then is the function of the inducer? Does it add a little piece of 

 structural information to the main information provided by the gene? Does 

 it select among several possibilities the folding corresponding to the active 

 enzyme? Does it pull the enzyme off^ the template? Does it control the 

 operation of the genetic locus or that of the assembly template in some 

 specific way? 



Sometimes, a variety of substances are able to induce the formation of the 

 same enzyme; these various inducers are structurally related to the sub- 

 strate of the enzyme. Thus ^-galactosidase synthesis in E. coli (Monod etal., 

 1951) or in B. megateriuni (Landman, 1957) can be induced by various 

 ^-galactosides or thiogalactosides, some of which are not split by the 

 enzyme. A comparable situation exists in the induction of a glucosidase in 

 yeast (Duerksen and Halvorson, 1959) and of penicillinase in B. cereus 

 (Pollock, 1956). In spite of differences of structure of the inducers, the 

 properties of the enzyme produced are always the same, although 



