Repression of the Shikimic Acid Pathway

Lack of Repression of the Shildmic Acid Pathway.—It is well established that a control mechanism on the shikimic acid pathway is by repression of enzymes early in the pathway by the end products, e.g. by phenylalanine. Cases where this type of control appear to have broken down have now been reported. Lowe and Westlake, in studying the biosynthesis of the phenolic antibiotic chloramphenicol in Streptomyces sp. 3022a, examined several enzymes of the pathway, notably chorismate mutase and anthranilate synthetase, but could find no evidence that end-product control on chloramphenicol synthesis was operating in this organism. Similarly, Chu and Widholm fed phenylalanine and tyrosine to a range of tissue cultures of higher plants, but were not able to observe any evidence of feedback control on chorismate mutase levels. 

In another case with higher plants, Baillie et alf deliberately tried to inhibit shikimate dehydrogenase with isonicotinic add derivatives, with the idea of using them as potential herbicides which would not be toxic to animals. Compounds based on l,6-dihydroxy-2-oxoisonicotinic add (6 effectively inhibited the enzyme in vitro, but attempts to use these compounds in vivo were foiled, probably because the inhibition was reversible and aromatic synthesis was not completely repressed. These inhibitors were anomalous in their behaviour, since they inhibited the enzyme in the back reaction (shikimate -+ NADP + dihydroshikimate), and had only little effect on the forward reaction.  

---