52 PerspecfJves In Microbiology 



DHS, and this compound has been found to inhibit com- 

 petitively the utilization of its own product, shikimic acid 

 (6). But this is probably a special case; I suspect that in- 

 activity of an externally added substrate is more frequently 

 based on a permeability problem, or, more generally speak- 

 ing, on inaccessibility of the compound to its enzyme with- 

 in the cell. Since this explanation for inactivity, when 

 offered by a biochemist, is generally shrouded with apolo- 

 gies for its ad hoc character, I should like to refer briefly to 

 some recent findings in the aromatic series that offer more 

 positive support for this view. 



These findings are based on the behavior of an Aero- 

 hacter mutant blocked before DHQ. This strain shows a 

 rather slow response to shikimic acid or DHS, and an even 

 slower, barely detectable response to DHQ. But from this 

 auxotroph one can select a secondary mutant that grows 

 rapidly on DHQ; and this strain is then found to grow 

 faster on DHQ than on DHS or shikimic acid, even in high 

 concentrations (12). The enzyme studies described have 

 convinced us, however, that (a) DHQ is an obligatory inter- 

 mediate in the wild type growing on glucose, and (b) in 

 functioning as such an intermediate (or as a growth factor 

 in an auxotroph), it must be transformed into DHS. 

 Furthermore, the enzyme that effects the transformation of 

 DHQ to DHS is found in just as high a concentration in 

 the primary auxotroph as in the wild type (24), even though 

 the auxotroph can hardly grow on DHQ. 



We are therefore forced to conclude that in the primary 

 auxotroph, externally added DHQ cannot easily get to its 

 enzyme, and in the secondary mutant this barrier has been 

 eliminated. Furthermore, since this secondary mutant 

 grows faster on DHQ than on its product, DHS, it seems 

 clear that in this strain a partial accessibility barrier is still 

 present for externally added DHS, in contrast to the DHS 

 formed endogenously from added DHQ. 



Although these findings do not constitute direct evidence 



