Chorismate regulation

Of the separately compartmented isozyme pairs that exist for DAHP synthase, chorismate mutase, and anthranilate synthase, each isozyme member of a given pair has different properties of regulation and other distinctive characteristics (see Tables I and II). This suggests a high probability that each isozyme is the gene product of a different gene. 

For the aromatic pathway (Figure 30.20), the critical control points are the condensation of phosphoenolpyruvate and erythrose-4-phosphate to 3-deoxy-D-arabinoheptulosonate 7-phosphate, DAHP, by DAHP synthase. For tryptophan, the formation of anthranilic acid from chorismic acid by anthranilate synthase is the second critical control point. The transcriptional regulation was overcome through the use of alternative promoters and allosteric regulation was circumvented by the classical technique of selection for feedback-resistant mutants using toxic analogues of the repressing compounds. 

A novel mechanism for regulating transcription in bacteria was discovered by Charles Yanofsky and his colleagues as a result of their studies of the tryptophan operon. The 7-kb mRNA transcript from this operon encodes five enzymes that convert chorismate into tryptophan (Section 24.2.10). The mode of regulation of this operon is called attenuation, and it... 

The aroF gene lies in an operon with tyrA, which encodes the bi functional protein chorismate mutase/prephenate dehydrogenase. Both genes arc regulated by the TyrR repressor protein complexed with tyrosine. The aroF gene product accounts for 80% of the total DAHP synthase activity in wild-type F. coli cells. 

Amino acid biosynthesis is often regulated by the end products of a given pathway to control the relative amounts of amino acids being produced. Aromatic amino acid biosynthesis thus far is known to be feedback regulated at three points in the shikimate/chorismate pathway. The initial step is catalyzed by 3-deoxy-D-arabino-2-heptulosonate-7-... 

Enzymes catalyzing the conversions from chorismate (37), namely, CM and anthranilate synthase (AS) (Figure 6), are also subject to feedback regulation. CM is inhibited by Phe (1) and Tyr (2), and activated by... 

In contrast to E. coli, Flavobacterium [112] is unable to grow anaerobically and does not seem to produce a catechol siderophore from isochorismic acid. Regulation of isochorismic acid synthesis is therefore likely to be completely different. The relative high K , value of isochorismate synthase for chorismic acid, compared to E. coli, may prevent drainage of substrates into isochorismic acid-utilizing reactions. This may indicate that isochorismate synthesis is controlled not only at the level of transcription, as is the case in E. coli, but also at enzyme level [112]. 

S ATP + shikimate <3, 17, 19> (<3> SK2 is the isoenzyme that normally functions in aromatic biosynthesis in the cell, SKI functions only when high intracellular levels of shikimate occurs [3] <19> energy charge plays a role in regulating shikimate kinase, thereby controlling the shikimate pathway [10] <17> the enzyme catalyzes the committed step in the seven-step biosynthesis of chorismate [18]) (Reversibility <3, 17, 19> [3, 10, 18]) [3, 10, 18]... 

In this review we have only dealt with alkaloid biosynthesis in C. roseus the biochemistry of this plant has also been studied in detail for other aspects, such as anthocyanin production, phosphate metabolism, cell growth, and cell division cycle (e.g., ref. 362). Unfortunately, most of the studies concerning the primary metabolism are not linked with those of secondary metabolism. However, one may expect that in the future the studies on secondary metabolism, such as chorismate-derived products (an-thocyanins, benzoic acid derivatives, and alkaloids) and terpenoid-derived products such as the alkaloids, will be integrated. This will eventually allow us a much better insight into the overall biochemistry of the plant. All of the available information makes C. roseus an outstanding model system for the study of the regulation of plant metabolism. 

Fig. 6. Regulation of the synthesis of aromatic amino acids in plants. Each of the sequential arrows represents the enzyme catalyzed steps detected in Figs. 2, 3 and 4. Bold lines indicate inhibition of chorismate mutase by phenylalanine and tyrosine in addition to anthranilate synthase inhibition by tryptophan. The dashed arrow symbolizes the ability of tryptophan to both activate chorismate mutase and antagonize inhibition of this enzyme by either phenylalanine or tyrosine.

Nelmstaedt. K. Krappmann, S. Braus, G.H. Allosteric regulation of catalytic activity Escherichia coli aspartate 38. transcarbamoylase versus yeast chorismate mutase. Microbiol. Mol. Biol. Rev. 2001. 63. 404-421. 

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