84 CONTROL MECHANISMS IN CELLULAR PROCESSES 



altered enzyme was also resistant to feedback control by the end 

 product so that in a glucose minimal medium, the end product was 

 excreted. 



While such organisms would not be expected to fare as well in 

 non-selective environments as organisms having effective control 

 mechanisms, they would be of value as the basis of microbial proc- 

 esses for the production of the excreted compound. Nevertheless, 

 industrial screening programs have resulted in the isolation from soil 

 of organisms which convert a substantial proportion of the carbon 

 source to an amino acid (Udaka, 1960). Another, more rational, 

 svstematic procedure was employed by Adelberg ( 1958 ) for obtain- 

 ing amino acid excretors. His method was to select organisms re- 

 sistant to amino acid analogs. Undoubtedly each procedure was 

 selecting organisms in which the initial enzyme in a biosynthetic 

 sequence was resistant to the end product of the sequence. 



Finally, a comment should be made on the relative physiological 

 role of the kind of control mechanism emphasized here. Certainly, 

 both repression and end-product inhibition are important regulatory 

 mechanisms. It would be assumed a priori that in terms of the syn- 

 thesis of small molecules, repression at best is a sluggish control 

 mechanism. It would function to provide for preferential utiliza- 

 tion of an exogenous supply of a metabolite only following a dilution 

 of the pre-existing enzvmes by growth. In contrast, one would ex- 

 pect end-product inhibition of the action of an enzyme to occur 

 immediately and provide for complete preferential utilization. For 

 the arginine pathwav, this distinction has been shown by Enis and 

 Gorini ( 1959) . Thev found, superimposed upon an extremely effec- 

 tive control by repression (feedback Loop I in Fig. 3-3), an even 

 m.ore delicate feedback control that could only be explained by as- 

 suming a mechanism like that represented by feedback Loop II in 

 Fig. 3-3. With this elegant demonstration, there would appear to 

 be little doubt about the relative roles of the two control mechanisms. 



References 



Abelson, p. H. 1954. Amino acid biosynthesis in Escherichia coli: isotopic competi- 

 tion with Ci^-glucose. /. Biul. Chem. 206: 335-343. 



Adelberg, E. A. 1958. Selection of bacterial mutants which excrete antagonists of 

 antimetabolites. /. Bacterial. 76: 326. 



Bonner, D. 1946. Further studies of mutant strains of Neurospora requiring iso- 

 leucine and valine. /. Biol. Chem. 166: 545-554. 



