Pyruvate-Based Pathway for Synthesis of 3-dehydroshikimate
Figure 1: (a) carbohydrate phosphotransferase; (b) KDPGal aldose, D-erythrose 4-phosphate; (c) DAHP synthase, D-erythrose 4-phosphate; (d) shikimate pathway enzymes.
3-dehydroshikimate, a highly versatile compound that is currently limitedly produced, is used in supporting the creation of novel treatments of influenza in addition to being the starting synthesis point of a large combinatorial library of molecules. However, the current process of making 3-dehydroshikimate is very slow and inefficient. Michigan State University researchers have discovered a method utilizing the Shikimate pathways in a way which eliminates and bypasses the reliance on other systems leading to the creation of a pyruvate-based shikimate pathway able to increase yields for both 3-dehydroshikimate and its intermediates.
Description of the Technology:
The invention provides the methods for the creation of a pyruvate-based pathway to support microbial growth and metabolism, growth rates and synthesis through use of the shikimic acid comprising enzyme-catalyzed condensation reaction creating 3-dehydroshikimate, which involves recombinant cells that encode enzymes for said process. Creation of 3-dehydroshikimate was made and found to circumvent the competition for phosphoenolpyruvate that is used in other systems that take higher priority over the Shikimate pathway, such as the carbohydrate and phosphotransferase system for microbial transport and phosphorylation of glucose. Previously limited yields of natural products are no longer limited with the use of this pyruvate derivative.
- 4 to 8 folds higher specific activities relative to using native enzymes
- Elimination of tedious multi-step isolation procedures from plants
- Plethora of different uses due to its chiral compound and high functionalized six-membered carbocyclic ring and multiple asymmetric centers
- Shikimic Acid is an attractive commercially valuable chiral compound useful in a variety of synthetic reactions
- Greater production of aromatic metabolites which provide UV protection, electron transport support, signaling molecules and serve as antibacterial agents
- Shikimic acid is a starting material in the synthesis of neuraminidase inhibitors effective in the treatment of influenza
- Creation of sustainable production of p-hydroxybenzoic acid
Issued patent US 8,372,621
Full licensing rights available
Journal of the American Chemical Society, 2004
Dr. John W. Frost
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Michigan State University