APPLICATIONS OF TECHNOLOGY:
Microbial production of
- Antioxidants, e.g., hydroxytyrosol
- Supplements, e.g., melatonin
- Medications, e.g., L-DOPA
- Inexpensive, consistent production with minimal impurities
- Independent of olive crop production and expensive chemical synthesis that produces toxic waste
- Modifiable to produce desired substances other than hydroxytyrosol: L-DOPA, serotonin, etc.
Taek Soon Lee and colleagues at Berkeley Lab have developed a method for using a microbial host to synthesize the powerful antioxidant and dietary supplement hydroxytyrosol. The method could be modified to produce other desirable oxidized products of aromatic amino acids, such as L-DOPA, melatonin, serotonin, and various alkaloid natural products.
The scientists transformed a strain of E. coli to express a group of enzymes and cofactors that efficiently convert tyrosine to hydroxytyrosol, a process that includes selective oxidation of tyrosine to L-DOPA. They optimized various steps in this pathway to minimize the quantity of side products. In particular, they engineered the process to avoid over-oxidation of tyrosine, which would produce melanin and other impurities, and to exclude the production of tyrosol, a less potent antioxidant that needs to be removed when purifying hydroxytyrosol.
Hydroxytyrosol is typically produced either by chemical or enzymatic hydrolysis of olive extracts or by chemical synthesis. Hydrolysis of extracts is subject to fluctuations in olive crop production and the significant challenges of separating and purifying the final compound. Chemical synthesis, on the other hand, is limited by the production of toxic organic wastes, the high cost of reagents, and the need for purification. The Berkeley Lab method overcomes these limitations and opens the door for efficient production of hydroxytyrosol and related products such as food supplements, pharmaceuticals, and starting materials used to synthesize other valuable compounds.
DEVELOPMENT STAGE: Bench scale production.
STATUS: Published PCT patent application, WO/2012/135389, available at www.wipo.int. U.S. Patent #10597685. Available for licensing or collaborative research.
FOR MORE INFORMATION:
Satoh, Y., Tajima, K., Munekata, M., Keasling, J. D., Lee, T .S. “Engineering of L-tyrosine oxidation in Escherichia coli and microbial production of hydroxytyrosol,” Metabolic Engineering, 14 (2012) 603-610.
REFERENCE NUMBER: EJIB-2939