Enzymic arrangement and allosteric regulation of the aromatic amino acid pathway in Neisseria gonorrhoeae.

Abstract

The pathway construction and allosteric regulation of phenylalanine and tyrosine biosynthesis was examined in Neisseria gonorrhoeae. A single 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase enzyme sensitive to feedback inhibition by L-phenylalanine was found. Chorismate mutase and prephenate dehydratase appear to co-exist as catalytic components of a bifunctional enzyme, known to be present in related genera. The latter enzyme activities were both feedback inhibited by L-phenylalanine. Prephenate dehydratase was strongly activated by L-tyrosine. NAD+-linked prephenate dehydrogenase and arogenate dehydrogenase activities coeluted following ion-exchange chromatography, suggesting their identity as catalytic properties of a single broad-specificity cyclohexadienyl dehydrogenase. Each dehydrogenase activity was inhibited by 4-hydroxyphenylpyruvate, but not by L-tyrosine. Two aromatic aminotransferases were resolved, one preferring the L-phenylalanine:2-ketoglutarate substrate combination and the other preferring the L-tyrosine: 2-ketoglutarate substrate combination. Each aminotransferase was also able to transaminate prephenate. The overall picture of regulation is one in which L-tyrosine modulates L-phenylalanine synthesis via activation of prephenate dehydratase. L-Phenylalanine in turn regulates early-pathway flow through inhibition of DAHP synthase. The recent phylogenetic positioning of N. gonorrhoeae makes it a key reference organism for emerging interpretations about aromatic-pathway evolution.