The Aminoshikimate pathway is a biochemical pathway present in some plants, which has been studied by biologists, biochemists and especially those interested in manufacture of novel antibiotic drugs. The pathway is a novel variation of the
shikimate
Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower ''sh ...
pathway. The aminoshikimate pathway was first discovered and studied in the
rifamycin
The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium ''Amycolatopsis rifamycinica'' or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective again ...
B producer ''
Amycolatopsis
''Amycolatopsis'' is a genus of high GC-content bacteria within the family Pseudonocardiaceae.
The genus is known for producing many types of antibiotics, including
* Epoxyquinomicin, related to ''Amycolatopsis sulphurea'', are a class of weak ...
mediterranei''. Its end product, 3-amino-5-hydroxybenzoate, serves as an initiator for polyketide synthases in the biosynthesis of
ansamycin
Ansamycins is a family of bacterial secondary metabolites that show antimicrobial activity against many Gram-positive and some Gram-negative bacteria, and includes various compounds, including streptovaricins and rifamycins. In addition, these c ...
s.
Overview
Floss and coworkers identified the gene cluster associated with the aminoshikimate pathway in ''Amycolatopsis mediterranei''. The enzyme-catalyzed condensation of 1-deoxy-1-imino-
D-erythrose 4-phosphate with phosphoenolpyruvate to form 4-amino-3,4-dideoxy-
d-arabino-heptulosonic acid 7-phosphate has been proposed to be the first committed step in the aminoshikimate pathway. Guo and Frost demonstrated that the unusual metabolite, 1-deoxy-1-imino-
D-erythrose 4-phosphate, is derived from 3-amino-3-deoxy-
D-fructose 6-phosphate. In addition, kanosamine biosynthesis has been directly implicated by Guo and Frost as the source of the aminoshikimate pathway's nitrogen atom.
Uses
Aminoshikimate pathway has been assembled in ''E. coli'' to synthesize
aminoshikimic acid, which is a promising starting material for the synthesis of antiinfluenza agent
oseltamivir
Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at h ...
(brand name Tamiflu).
References
{{reflist, 2
Metabolic pathways