Neurospora tryptophan biosynthesis

Anthranilic acid and indole are precursors of tryptophan in numerous microorganisms and fungi (e.g., 5, 263, 264, 602, 741, 783, 785, 816, 854, 855, 876), and it is probable that anthranilic acid is derived, with intermediate steps, from the common precursor, CP of diagram 1. The conversion of anthranilic acid to indole and tryptophan has been shown unambiguously in Neurospora with the use of isotopic techniques (93, 663). There may, however, be other pathways for tryptophan biosynthesis (45, 702). Tryptophan can, for example, be formed by transamination of indolepyruvic acid (e.g., 470, 912), which might be formed other than via anthranilic acid. Thus aromatic-requiring mutants have been found which accumulate unidentified indole compounds (307). 

Fig. 7. Intermediates and gene-enzyme relationships of tryptophan biosynthesis in Neurospora. Abbreviations PRPP, 5-phosphoribosyl-l-pyrophosphate PRA, N-(5 -phosphoribosyl) anthranilic acid CDRP, l-(o-carboxyphenylamino)-l-deoxyribulose-5-phosphate InGP, indole-3-glycerolphosphate PR, phosphoribosyl.

The shikimate pathway was identified through the study of ultraviolet light-induced mutants of E. coli, Aerobacter aerogenes, and Neurospora. In 1950, using the penicillin enrichment technique (Chapter 26), Davis obtained a series of mutants of E. coli that would not grow without the addition of aromatic substances.4 5 A number of the mutants required five compounds tyrosine, phenylalanine, tryptophan, p-aminobenzoic acid, and a trace of p-hydroxybenzoic acid. It was a surprise to find that the requirements for all five compounds could be met by the addition of shikimic acid, an aliphatic compound that was then regarded as a rare plant acid. Thus, shikimate was implicated as an intermediate in the biosynthesis of the three aromatic amino acids and of other essential aromatic substances.6 7... 

Yanofsky, C. and Rachmeler, M. (1958) The exclusion of free indole as an intomediate in the biosynthesis of tryptophan in Neurospora crassa. Biochim. Biophys. Acta 28, 640-641. 

Early studies of the biosynthesis of L-tryptophan (3) established that both anthranilic acid and indole were able to replace L-tryptophan as a growth factor for some bacteria. The suggestion that these compounds were normal precursors of the aromatic amino acid was confirmed by Tatum, Bonner and Beadle " who showed that some L-tryptophan requiring mutants of Neurospora sp. responded to anthranilic acid or indole whilst others responded only to indole and accumulated anthranilic acid. Somewhat later other mutants were found which were blocked between indole and L-tryptophan and accumulated indole in the culture medium. 

The simplest explanation is that the gene collaborates in the production of the enzyme which catalyzes the particular metabolic reaction. In the above diagram, the gene v+ of Drosophila controls the production of the enzyme which effects the conversion of tryptophan to kynurenine the gene cn+ (Drosophila) or Y 31881+ (Neurospora) controls the biosynthesis of the enzyme kynurenine hydroxylase. In some cases it could be demonstrated that the mutant indeed lacked the enzyme. Occasionally it is replaced by a very similar, but enzymically inactive, protein. 

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