72 NITROGEN METABOLISM 



acid. Growth of 10575 i^ the presence of limiting amounts of 

 tryptophan resulted in the appearance in the medium of a 

 substance supporting the growth of 40008. This material, 

 presumably the substrate of the blocked reaction, was later 

 isolated and identified as anthranilic acid. The reaction 

 sequence is therefore anthranilic acid — >■ indole — > trypto- 

 phan. The rate of uptake of indole by 10575 was found to 

 be a function of the concentration of L-serine in the medium, 

 and after growth had ceased tryptophan was excreted into 

 the medium. The enzyme forming tryptophan by the con- 

 densation of serine with indole was studied in cell-free 

 homogenates of Neurospora mycelia and shown to con- 

 tain a prosthetic group of pyridoxal phosphate [49]. The 

 mechanism by which anthranilic acid is converted into 

 indole remains unknown. By using isotopes it has been 

 shown that the carboxyl group of the former does not give 

 rise to any of the carbon in the indole nucleus of trypto- 

 phan [37«]. 



A detailed investigation of Neurospora mutants able to 

 grow on tryptophan or nicotinic acid has confirmed the 

 conclusion drawn from animal nutrition experiments that 

 the metabolism of these two compounds is interrelated. 

 Furthermore, Haskins and Mitchell have proposed that, at 

 least in Neurospora, there is a 'tryptophan cycle' [24]. By 

 using the appropriate mutants and growth conditions, 

 3-hydroxyanthranilic acid, kynurenine and quinolinic acid 

 have all been isolated from culture filtrates. Like Lb. 

 arabinosus, the growth of some, but not all, nicotinic acid 

 auxotrophs of Neurospora is supported by quinolinic acid, 

 although only in high concentrations [21]. It is therefore 

 possible that quinolinic acid is a by-product derived from 

 the substrate of a blocked reaction, rather than a direct 

 intermediate in the synthesis of nicotinic acid. 



Certain mutants of A^. crassa and Esch. colt require tryp- 

 tophan, phenylalanine, tyrosine and ^-aminobenzoic acid 

 (PAB), all in large amounts, before there is even slow 

 growth, indicating that these four compounds may be 

 derived from a common precursor and that the synthesis 

 of anthranilic acid and tryptophan is connected with the 



