50 Perspectives In Microbiology 



compounds (A and B) into one or more essential metabolic 

 products (Xp X2 . . . )' (b) ^h^t a single enzyme that con- 

 verts A to B is demonstrable in extracts of the wild-type 

 organism; ^ and (c) that this enzyme is absent or inactive in 

 the extracts of a mutant strain that has lost the ability to 

 form Xi, X2 . . . from the source materials O^, O2 . . . 

 These criteria can be extended, of course, to include 

 chemical rather than genetic elimination of the activity of 

 an enzyme, provided that the effect of the inhibitor is re- 

 stricted to a single enzyme. 



Accepting these criteria, I think we can feel quite certain, 

 on the basis of the enzymatic evidence presented, that 

 DHQ, DHS, and shikimic acid are true normal intermedi- 

 ates in aromatic biosynthesis, and almost certain that PPA 

 and phenypyruvic acid are normal intermediates in the 

 synthesis of phenylalanine. The structure of PPA also sug- 

 gests it as a likely precursor of tyrosine, and this possibility 

 is supported by the fact that PPA is accumulated by some 

 tyrosine auxotrophs. Until an enzymatic connection be- 

 tween PPA and tyrosine is established, however, we cannot 

 be sure of this path. 



The positions of phosphoshikimic acid and compound 

 Zl are uncertain, since there are as yet no enzymatic studies 

 on these compounds. Accumulation studies have already 

 shown that Zl arises after shikimic acid and phosphoshi- 

 kimic acid, but it may be either a direct member of the 

 chain or a side product. Phosphoshikimic acid I would pro- 



4 Though in many cases an enzyme can carry out the same type of 

 reaction on a variety of substrates, each of these usually gives rise to a 

 different product; hence the assumption is made here that the essential 

 enzyme that forms B from A can form B only from A. But this assump- 

 tion may conceivably not be true (compare aconitase, a presumably single 

 enzyme that can form aconitate from either citrate or isocitrate). It is 

 therefore desirable to strengthen the evidence that A and B are the true, 

 physiological substrate and product of an essential enzyme by showing 

 further that they in turn are formed and utilized, respectively, by other 

 essential enzymes in the same biosynthetic sequence. 



