Neurospora tryptophan synthesis

Among different organisms the five enzyme activities required for tryptophan synthesis are distributed on different proteins (table 21.1). For example, in E. coli, indoleglycerol phosphate synthase catalyzes both the isomerization of phosphoribosylanthranilate and the cyclization step. Of particular interest is the occurrence of a single protein of the catalytic activities for nonconsecutive reactions in some cases. If in such cases the proteins were separate from each other in the cell, this arrangement, for example, in Neurospora, would necessitate the product of one reaction leaving the product site of one enzyme to be acted on by another... 

What may be called the 3-deoxy-D-om6mo-heptulosonic acid 7-phosphate pathway is used in E. coli for the synthesis of (a) the aromatic amino acids of proteins and (b) p-aminobenzoate. In Neurospora this pathway is also used for the synthesis of niacin ( > since these organisms convert tryptophan to niacin by a pathway first observed in mammals, but E. coli synthesizes niacin by a different pathway. jt is clear at present, even on the basis of limited evidence, that plants use the 3-deoxy-D-oroWno-heptulosonic acid 7-phosphate pathway for the synthesis of a much more extensive series of products. 

Mitchell, H. K. and J. Lein. 1948. A Neurospora mutant deficient in the enzymatic synthesis of tryptophan. J. Biol. Chem. 175, 481-482. 

NAD is reutilized to synthesize more NAD Hie P. n. c. probably operates in all organism whether or not they are capable of synthesizing the pyridine ring system, and irrespective of the pathway of synthesis (from L-tryptophan in animals, Neurospora and Xan-thomonas pruni from aspartate and dihydroxyace-tone phosphate in plants and most bacteria). 

Synthesis of tryptophan from indole and serine has been demonstrated in Neurospora " and E. coli. Further investigation has shown that... 

Pyridoxal phosphate has been established as a coenzyme in two reactions involving tryptophan. An enzyme has been isolated from Neurospora which catalyzes a synthesis of tryptophane from serine and indole. This reaction requires pyridoxal phosphate. An enzyme has been isolated from E. coli which causes the decomposition of tryptophan to pyruvic acid, indole, and ammonia here too pyridoxal phosphate is a necessary cofactor. 

Synthesis of Tryptophan from Indole and Serine, Tatum and Bonner reported that a mutant of Neurospora crassa could utilize indole in place of tryptophan. Umbreit, Wood, and Gunsalus, by using extracts from this mutant, showed that, with pyridoxal phosphate as a coenzyme, tryptophan was synthesized from serine and indole via the following reaction ... 

These studies were confirmed by tracer experiments showing that nitrogen of nicotinic acid (formed by Neurospora) is derived from 3-hydroxyanthranilic acid (478). Experiments with doubly labeled tryptophan demonstrate that tryptophan is probably the only source of quinolinic acid in rat metabolism (645) and that carbon atom 3 of tryptophan, the precursor of the carboxyl carbon of 3-hydroxyanthranilic acid, becomes carboxyl carbon in nicotinic acid (310,340,341,373). In vitro studies of the enzymic oxidation of 3-hydroxyanthranilic acid confirm its relationship to quinolinic acid (498) and show that picolinic acid may also form from it (539,540) but nicotinic acid synthesis under... 

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