38. BIOSYNTHESIS OF PROTEINS IN BACTERIAL CELLS 433 



sis of all the enzymes will then become impossible. But the strain is geneti- 

 cally unable to make guanine from any simple carbon source, and no endoge- 

 nous guanine will be formed. Therefore since guanine represses the enzymes 

 for its own biosynthesis, these enzymes will be synthesized after guanine 

 starvation. This state of affairs is observed for inosinic dehydrogenase, 

 which is synthesized in the absence of guanine whatever the nature of the 

 carbon source is. Inositol dehydrogenase, on the other hand, is generally 

 induced by inositol in the wild strain, which means according to recent 

 hypotheses on enzyme induction, 140 that inositol can antagonize the cyto- 

 plasmic repressor of inositol dehydrogenase. Therefore, since the effects of 

 the repressor for inositol dehydrogenase, which is accumulated by A . aero- 

 genes during guanine starvation, are neutralized by inositol, the strain not 

 only manufactures inosinic dehydrogenase (for the reasons cited above) but 

 also the inositol dehydrogenase. 



Similar results have been obtained by Pardee. 141 Thus pyrimidine mutants 

 of E. coli, in the absence of their essential base, produce very large quantities 

 of the enzymes involved in pyrimidine biosynthesis (ureidosuccinate syn- 

 thetase, dihydroorotate dehydrogenase) (see Chapter 36). The level of these 

 enzymes during pyrimidine starvation can reach 10 to 100 times that ob- 

 served in the normal strain. 



All the above results taken together indicate that in the absence of RNA 

 synthesis, the cell can manufacture enzymes whose repression is not pos- 

 sible under the conditions of the experiment. 



Preferential synthesis of enzyme in the absence of RNA synthesis can 

 also be observed during diauxic growth. It is known from the work of 

 Monod, 96 that when E. coli is cultivated in the presence of a mixture of 

 glucose and of another carbon source, the utilization of which requires 

 "adaptation," the cell grows first at the expense of glucose which is con- 

 stitutively metabolized. When glucose is exhausted there is a phase of very 

 slow growth during which the cell adapts itself to the second carbon source, 

 followed by a phase of rapid growth at the expense of this carbon source. 

 During the intermediate phase the cell elaborates no RNA, but increases 

 its protein content by 30%, and synthesizes the enzymes involved in the 

 utilization of the second carbon source. 139 



b. Effect of Base Analogs on the Synthesis of Bacterial Enzymes 



The discovery that certain base analogs (see Chapter 39) can be incor- 

 porated into the RNA of bacteria, of animal cells, and of plant viruses 142-145 



140 A. B. Pardee, F. Jacob, and J. Monod, Compt. rend. acad. sci. 246, 3125 (1958). 



141 A. B. Pardee, quoted by B. Magasanik in Ann. Rev. Microbiol. 2, 221 (1953). 



142 J. Monod, "Recherches sur la croissance des cultures bacteriennes." Herman et 

 Cie, Paris, 1942. 



