L-Tryptophan biosynthesis

In what sense may indole be viewed as an intermediate in L-tryptophan biosynthesis ... 

Somerville, R. L., Tryptophan Biosynthesis, regulation, and large-scale production, in Amino Acid Biosynthesis and Genetic Regulation, Herrmann, K. M. and Somerville, R. L., Eds., Addison-Wesley, Reading, MA, 1983, 351-378. 

RADWANSKI, E.R., LAST, R.L., Tryptophan biosynthesis and metabolism Biochemical and molecular genetics. Plant Cell, 1995,7, 921-934. 

For further investigation of L-tryptophan biosynthesis, labelled antbranilate waus used. C-labelled anthranilic acid is converted uniformly to L-tryptophan in plant tissues. Furthermore, labelled lAA was formed from 3- 0-L-tryptophan. Both metabolic sequences are subject to interference by indole metabolites (intermediates of lAA biosynthesis) and by phenols. p-Coumario acid - one of the phenolic substances that inhibit cell elongation - depresses the formation of tryptophan from C-anthra-nilic acid, whereas caffeic acid, which enhances cell elongation, stimulates the incorporation of anthranilic acid into tryptophan (Table 2). Thus, one control effect in the action of phenols on plant growth may be influence on L-tryptophan biosynthesis. 

The regulation of L-tryptophan biosynthesis has been most closely studied in Escherichia In other micro-organisms... 

Chan, E.C., Tsai, H.L., Chen, S.L., and Mou, D.G. (1993) Amplification of the tryptophan operon gene in Escherichia coli chromosome to increase L-tryptophan biosynthesis. Appl Microbiol Biotechnol, 40, 301-305. 

The amino acid precursor for 5-HT, L-tryptophan, increases the biosynthesis 5-HT and, therefore, has been investigated for potential antidepressant properties, but with mixed results (Green and Costain, 1979). It was withdrawn in 1990, following a number of fatal cases of eosinophilia myalgia (a disorder characterised by severe muscle pain and abnormally high levels of one type of white blood cell, the eosinophil) in individuals principally using it as a natural hypnotic. 

Independently, in 1998, the Cordell (290,379,380) and Pearce (381) groups published some preliminary biosynthetic results on staurosporine and rebeccamycin, typical representative members of the indolo[2,3-fl]pyrrolo[3,4-c]carbazole alkaloids. Cordell s biosynthetic studies on staurosporine were based on feeding experiments with L-tryptophan. These studies showed that two units of L-tryptophan, with the two carbon side-chains intact, were responsible for the biosynthesis of staurosporine aglycone. Further experimental studies are necessary to establish the nature of the intermediate in the biotransformation of L-tryptophan to staurosporine. Although these studies are not complete, they gave for the first time insight into the biosynthesis of staurosporine (379,380). 

The shikimate/arogenate pathway leads to the formation of three aromatic amino acids L-phenylalanine, L-tyrosine, and L-tryptophane. This amino acids are precursors of certain homones (auxins) and of several secondary compounds, including phenolics [6,7]. One shikimate/arogenate is thought to be located in chloroplasts in which the aromatic amino acids are produced mainly for protein biosynthesis, whereas the second is probably membrane associated in the cytosol, in which L-phenylalanine is also produced for the formation of the phenylpropanoids [7]. Once L-phenylalanine has been synthesized, the pathway called phenylalanine/hydroxycinnamate begins, this being defined as "general phenylpropanoid metabolism" [7]. 

Anthranilic acid (Figure 6.106) is a key intermediate in the biosynthesis of L-tryptophan (see page 126) and so contributes to the elaboration... 

The biosynthesis of 1 follows a pattern seen for all bisindoles that have been biosynthetically investigated thus far [17, 163, 164] two molecules of L-tryptophan (123) are oxidized and then dimerized to give an initial bisindole skeleton (Fig. 24). Historically, the biosynthesis of staurosporine (121) has been investigated in parallel with that of rebeccamycin (124), a related bisindole. Both molecules are thought to be biosynthesized through nearly identical routes to give the aglycone... 

Overall, the biosynthesis of 160 is characterized by the dimerization of 168 to give the central structure of the molecule. This head-to-tail dimerization strategy is efficient, using the same substrate twice, and is a sensible route, given the existence of the shikimate pathway, which provides, in turn, a precursor to 168. An analogous dimerization route can be seen for the biosynthesis of K252c (1), described in Sect. 5, where two molecules of indole-3-pyruvic acid imine (125), derived in turn from L-tryptophan (123), are dimerized to give an intermediate that leads to chromopyrrolic acid (128). In both cases, the monomer precursors, either 168 or 125, serve as both nucleophiles and electrophiles, and are activated to react by the presence of the appropriate enzymes. 

The catabolism of d- and of L-tryptophan in P. aureofaciens is different.67 Only the latter isomer is catabolized by the kynurenine pathway, and it also induces the enzymes of this pathway. Added L-tryptophan may then be catabolized by this pathway. That which is will not be available for biosynthesis of pyrrolnitrin. In support, a mutant that lacks the first enzyme of this catabolic pathway showed a 30-fold increase in the production of pyrrolnitrin as compared to normal organisms.67 D-Tryptophan, not suffering catabolism in this way, will be more readily available, through slow conversion into L-tryptophan, for biosynthesis of... 

The enzyme responsible for the first step in the biosynthesis of these alkaloids is DMAT synthase. This enzyme, which brings about the condensation of L-tryptophan with DMAPP, has been isolated from C. purpurea cultures. 

Indolmydn.—Previous evidence on the biosynthesis of indolmycin (88) in Strepto-myces griseus cultures accords with the pathway shown in Scheme 4. The first two steps in the pathway have been carried out using cell-free extracts of 5. griseus - and recent work has led to the isolation of two enzymes which can effect these transformations. The first, tryptophan transaminase, catalysed the pyridoxal phosphate-dependent transamination of L-tryptophan, but not D-trptophan, and in common with some other microbial transaminases, a-ketoglutarate was an efficient amino-group acceptor. L-Phenylalanine, tyrosine, and 3-methyltryptophan (this compound inhibited enzyme function) also underwent transamination. 

The steps of prenylation and dehydrogenation which follow (94) in the biosynthesis of these neoechinulins is unknown but from knowledge of echinulin biosynthesis (Scheme 6) introduction of the side chain at C-2 may be the next step. Prenylation of the benzene unit seems, by inspection of structures (97) through (101), to depend on C-8—C-9 unsaturation rather than the structure of the dioxo-piperazine ring. The stereochemistry of the desaturation reaction has been explored with L-tryptophan (85) samples stereospecifically labelled with tritium at... 

The L-tryptophan produced by Showa Denko K. K. was manufactured by fermentation using the bacterium Bacillus amyloliquefaciens. The biosynthetic pathway of L-tryptophan is shown in Figure 1. Several new strains (I-V), each modified slightly to increase the biosynthesis of tryptophan, were introduced sequentially during the years preceding the outbreak of EMS (Table 1). 

In summary, after feeding the stable isotope labeled compounds to V. hilgendotfii, LC/ESI-TOF-MS analyses of Cypridina luciferin extracted from the specimens strongly suggested that three amino acids of L-tryptophan, L-arginine and L-isoleucine participate in biosynthesis of Cypridina luciferin (Scheme 1). 

Oba Y, Kato S, Ojika M, Inouye S. Biosynthesis of luciferin in the sea firefly, Cypridina hilgendotfii L-tryptophan is a component in Cypridina luciferin. Tetrahedron Lett 2002 43 2389-92. 

BIOSYNTHESIS OF VARGUIA HILGENDORFIILUCIFERIN, ARISEN FROM L-ARGININE, L-TRYPTOPHAN, AND L-ISOLEUCINE... 

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