Final Stages in 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). 

Haskins and Mitchell (365) found that a Neurospora mutant blocked between anthranilic acid and tryptophan accumulated anthranilic acid when 

Partridge and co-workers (663) showed that such a cycle plays no part under conditions of normal tryptophan synthesis, and Adelberg (4) has plausibly ascribed the original results to adaptive formation of the enzyme kynureninase (discussed in detail later) induced by the high tryptophan content of the medium. 

The conversion of indole to tryptophan has been much more extensively studied. This is brought about by direct reaction of indole and serine under the influence of the enzyme tryptophan desmolase (better named tryptophan synthetase) (302, 853, 854) which requires p5U-idoxal phosphate as a coenzyme (890). The enzyme has been obtained in the cell-free state (890) and partially purified (965) and its genetics in Neurospora studied in detail (966). Zinc appears to play some part in tryptophan desmolase formation or function (628). 

The mechanism of function of pyridoxal phosphate in tryptophan biosynthesis is considered in more detail later in discussing other pyridoxine-dependent enzymes. An activated form of serine is formed which reacts with indole. Dehydration can take place in two ways intermolecularly, involving loss of water between the jS-hydroxyl of activated serine and the d-hydrogen of indole, or intramolecularly, involving loss of water from activated serine to give activated aminoacrylic acid, which then adds on to the i8-position of indole. Tatum and Shemin (858) in ingenious experiments 

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