Metabolic engineering for microbial production of shikimic acid.

Metab Eng

DSM Biotech GmbH, Karl-Heinz-Beckurts-Strasse 13, D-52428 Jülich, Germany.

Published: October 2003

AI Article Synopsis

  • Shikimic acid is a valuable compound used to create the antiviral drug Tamiflu, which treats infections.
  • It's more efficient to produce shikimic acid through fermentation using genetically engineered E. coli rather than extracting it from Illicium plants.
  • Strategies to improve production include modifying carbon uptake, regulatory pathways, and central metabolism to increase yields and reduce unwanted by-products.

Article Abstract

Shikimic acid is a high valued compound used as a key starting material for the synthesis of the neuramidase inhibitor GS4104, which was developed under the name Tamiflu for treatment of antiviral infections. An excellent alternative to the isolation of shikimic acid from fruits of the Illicium plant is the fermentative production by metabolic engineered microorganisms. Fermentative production of shikimic acid was most successfully carried out by rational designed Escherichia coli strains by blocking the aromatic amino acid pathway after the production of shikimic acid. An alternative is to produce shikimic acid as a result of dephosphorylation of shikimate-3-phosphate. Engineering the uptake of carbon, the regulatory circuits, central metabolism and the common aromatic pathway including shikimic acid import that have all been targeted to effect higher productivities and lower by-product formation are discussed.

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http://dx.doi.org/10.1016/j.ymben.2003.09.001DOI Listing

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