BIOSYNTHESIS OF AMINO ACIDS 271 



acid and a-amino-e-hydroxycaproic acid serve as precursors of lysine, 

 probably both being converted to a semialdehyde (475, 611). Since 

 Ophiostoma multiannulatiim lysineless mutants utilize a-ketoadipic 

 acid, it is probable that this compound is the precursor of a-aminoadipic 

 acid (54). 



A series of investigations of histidineless mutants of Neurospora 

 crassa is reviewed by Ames (20); the following over-all pathway is sug- 

 gested: 



Imidazole glycerol phosphate — > imidazole acetol phosphate — > 



L-histidinol phosphate -» L-histidine (14) 



Conventional nutritional techniques were of limited use in these 

 studies, since the phosphorylated intermediates do not penetrate the 

 cell. More reliance was placed on isolation of intermediates from 

 blocked mutants and on direct enzymatic studies (20, 21). 



The known early steps of the conversion of glucose to aromatic com- 

 pounds have been diagrammed in Chapter 6. Figure 10 takes up the 

 story from shikimic acid on; although this presentation is based in large 

 part on studies of Escherichia coli, all of the available evidence from 

 Neurospora crassa is in agreement with it. In particular, a multiple 

 requirement for p-aminobenzoic acid, phenylalanine, tyrosine, and 

 tryptophan is met by shikimic acid (526). Additional evidence is 

 found in the accumulation of prephenic acid by a strain deficient for 

 the three aromatic amino acids (361), and in the replacement of 

 tyrosine by phenylpyruvic acid (125). 



The suggestion that a-phenylglycine is a precursor of tyrosine and 

 phenylalanine (222) has not been borne out by later work (124). 



Tryptophan synthesis from anthranilic acid and indole by Neuro- 

 spora crassa is indicated by nutritional responses of deficient mutants 

 (66, 171, 525) and by studies with isotopic nitrogen (408). The con- 

 version of indole to tryptophan is catalyzed by tryptophan synthetase 

 (indole-serine ligase); this enzyme has been isolated and partially puri- 

 fied from N. crassa (616). The over-all reaction, which requires pyri- 

 doxal phosphate, may be written: 



Indole + serine —> tryptophan + H 2 (15) 



The mechanism of this reaction is considered by Tatum and Shemin 

 (528). Tryptophan synthesis in Claviceps purpurea is probably effected 

 by the same system (548). 



Presence or absence of the enzyme is controlled by a single gene in 



