Aminoshikimate pathway explained

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 pathway. The aminoshikimate pathway was first discovered and studied in the rifamycin B producer Amycolatopsis mediterranei. Its end product, 3-amino-5-hydroxybenzoate, serves as an initiator for polyketide synthases in the biosynthesis of ansamycins.[1]

Overview

Floss and coworkers identified the gene cluster associated with the aminoshikimate pathway in Amycolatopsis mediterranei.[2] 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.[3] In addition, kanosamine biosynthesis has been directly implicated by Guo and Frost as the source of the aminoshikimate pathway's nitrogen atom.[4]

Uses

Aminoshikimate pathway has been assembled in E. coli to synthesize aminoshikimic acid, which is a promising starting material for the synthesis of anti-influenza agent oseltamivir (brand name Tamiflu).[5] [6]

Notes and References

  1. Floss, H. G. . Natural products derived from unusual variants of the shikimate pathway. . Nat Prod Rep . 1997 . 14 . 433–452 . 10.1039/np9971400433. 9364776. 5 .
  2. August, P. R. . tang, L. . Yoon, Y. J. . Ning, S. . Muller, R. . Yu, T. -W. . Taylor, M. . Hoffmann, D. . Kim, C. -G. . Zhang, X. . Hutchinson, C. R. . Floss, H. G.. . Biosynthesis of the ansamycin antibiotic rifamycin: deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699 . Chem. Biol. . 1998 . 5. 2 . 69–79 . 10.1016/S1074-5521(98)90141-7 . 9512878 . free .
  3. Guo, Jiantao . Frost, John . Biosynthesis of 1-Deoxy-1-imino-d-erythrose 4-Phosphate: A Defining Metabolite in the Aminoshikimate Pathway . J. Am. Chem. Soc. . 2002 . 124 . 528–529 . 10.1021/ja016963v. 11804477. 4 .
  4. Guo, Jiantao . Frost, John . Kanosamine Biosynthesis: A Likely Source of the Aminoshikimate Pathway's Nitrogen Atom . J. Am. Chem. Soc. . 2002 . 124 . 10642–10643 . 10.1021/ja026628m. 12207504. 36 .
  5. Guo, Jiantao . Frost, John . Synthesis of Aminoshikimic Acid . Organic Letters . 2004 . 6 . 1585–1588 . 10.1021/ol049666e. 15128242. 10 .
  6. Frost, John & Jiantao Guo.