Precursor-directed Biosynthesis of 5-Hydroxytryptophan
- 詳細技術說明
- Organism: E. coli. Target product and synonyms: 5-hydroxytryptophan, 5-HTP,Serotonyl, Telesol, 5-Hydroxyl-L-tryptophan Target identifier(s): CAS: [4350-09-8]The inventionis comprised of genetically modified organisms, which over-express 5-Hydroxytryptophan(5-HTP). 5-HTP is a naturalnon-proteinogenic amino acid that serves as a direct biosynthetic precursor tothe neurotransmitter serotonin. Deficient serotonin in the central nervoussystem is thought to be an important physiological factor for depression. 5-HTPhas been shown to be effective for the treatment of a variety of conditions,including depression, insomnia, chronic headaches and binge eating associatedwith obesity. At the same time, it has relatively few side effects. Thetherapeutic efficacy of 5-HTP is due to its ability to enhance the synthesis ofserotonin in the brain. 5-HTP is well absorbed from an oral dose and can easilycross the blood-brain barrier. In most European countries, 5-HTP is a commonlyprescribed drug for multiple treatment purposes; while in North America marketit is sold as an "over-the-counter" dietary supplement. Currently,5-HTP is obtained through extraction from the seeds of Griffonia simplicifolia, a woody climbing shrub grown in Africa.The season- and region-dependent supply of the raw materials has been largelylimiting its cost-effective production and broad clinical applications. Inaddition, Griffonia derived 5-HTP hasbeen contaminated with a compound called Peak X, leading to the USDA brieflyremoving the supplement from shelves in the US. The current bulk wholesaleprice for 5-HTP ranges from 400 to 1000 USD/kg. Yet despite the current highproduction cost and limited supply, the global market of 5-HTP is still about50,000 kg (bulk value 20-50 million dollars).
- *Abstract
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The inventionprovides compounds, compositions, non-naturally occurring organisms, andmethods useful for production of 5-hydroxytryptophan (5-HTP) in a microbialcell. A microbial system which includes at least one microbial cell, such as abacterial cell or a yeast cell, is genetically engineered to express all or aportion of non-naturally occurring biosynthetic pathway that catalyzes theconversion of a simple carbon source, such as glucose, to 5-HTP. The inventioncan result in improved titers of 5-HTP and permits low-cost, large scaleproduction. Methods of making and using the genetically engineered cells arealso included in the invention.
References and Intellectual Property:
US Patent 9,663,768
Sun, X., Lin, Y., Yuan, Q., & Yan, Y.,Precursor-directed biosynthesis of 5-hydroxytryptophan using metabolicallyengineered E. coli. ACS Synthetic Biology 2015; 4:554-8
- 國家/地區
- 美國
