434 F. GROS 



has led to a study of the effect of these analogs on protein and enzyme for- 

 mation in bacteria. 



5-Hydroxyuridine and 8-azaguanine 146 inhibit the induction of /S-galac- 

 tosidase in E. coli without affecting appreciably its growth. Similar results 

 have been obtained with 8-azaguanine and 2,6-diaminopurine in Staphy- 

 lococcus aureus, where the analog inhibits the formation of inducible en- 

 zymes (catalase, galactosidase) rather than that of the constitutive enzymes 

 or enzymic systems (glucose oxidase). 147148 



These results must be related to the observations of Gale and Folkes 149 

 that in disrupted staphylococci, induced synthesis of /3-galactosidase can 

 be stimulated by a mixture of purines and pyrimidines and that after re- 

 moval of the RNA from the preparation, constitutive synthesis of catalase 

 can be restored by complete RNA, while induced synthesis of /3-galactosi- 

 dase can only be restored by a mixture of bases. 



These observations have led to the conclusion that de novo synthesis of 

 a specific protein (enzyme) requires the synthesis of a specific RNA, and 

 that synthesis of constitutive enzymes is not affected by the analog because 

 it is controlled by a preexisting RNA specific for this constitutive enzyme. 



Such a conclusion, which is probably the most highly developed form of 

 theory on cosynthesis, is open to a series of objections. 



(1) As has been mentioned above, considerable enzyme synthesis is ob- 

 served in mutants starved of an essential purine or pyrimidine if the carbon 

 source is chosen so as to avoid repression of the enzymes concerned. 



(2) Since the early work on inhibition of enzyme synthesis by ana- 

 logs, 147 ' 148 many cases of selective inhibition of the formation of constitutive 

 enzymes have been reported: in E. coli, 5-hydroxyuridine, 150 and 5-fluoro- 

 uracil 151 inhibit the constitutive synthesis of /3-galactosidase as much as 

 the inducible synthesis. In both cases growth is considerably less affected 

 than is enzyme synthesis. In Bacillus cereus, constitutive synthesis of peni- 

 cillinase is selectively inhibited by 8-azaguanine, 152 to the same extent as is 

 inducible synthesis. 



143 R. E. F. Matthews, Nature 171, 1061 (1953). 



144 F. Weygand, A. Wacker, and H. Dellweg, Z. Naturforsch. 7b, 19 (1952). 



145 R. Jeener and J. Rosseels, Biochim. et Biophys. Acta 11, 438 (1953). 



146 S. Spiegelman, H. O. Halvorson, and R. Ben Ishai', in "A Symposium on Amino 

 Acid Metabolism" (W. D. McElroy and B. Glass, eds.), p. 1048. Johns Hopkins 

 Press, Baltimore, 1955. 



147 E. H. Creaser, Nature 176, 556 (1955). 



148 E. H. Creaser, Biochem. J. 64, 539 (1956). 



149 E. F. Gale and J. P. Folkes, Biochem. J. 59, 675 (1955). 



150 F. Gros, Francoise Gros, and S. Spiegelman, unpublished results (1954). 

 161 A. B. Pardee, personal communication (1958). 



152 H. Chantrenne, Rec. trav. chim. 77, 586 (1958). 



