Engineering of l-tyrosine oxidation in Escherichia coli and microbial production of hydroxytyrosol
| Autor: | Yasuharu Satoh, Taek Soon Lee, Masanobu Munekata, Jay D. Keasling, Kenji Tajima |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Tyrosine 3-Monooxygenase
Bioengineering Biology Protein Engineering medicine.disease_cause Applied Microbiology and Biotechnology Cofactor Hydroxylation Mice chemistry.chemical_compound Biosynthesis Escherichia coli medicine Animals Cloning Molecular Tyrosine Aldehyde oxidase Tetrahydrobiopterin Phenylethyl Alcohol Recombinant Proteins Glucose chemistry Biochemistry biology.protein Hydroxytyrosol Oxidation-Reduction Biotechnology medicine.drug |
| Zdroj: | Metabolic Engineering. 14:603-610 |
| ISSN: | 1096-7176 |
| Popis: | The hydroxylation of tyrosine is an important reaction in the biosynthesis of many natural products. The use of bacteria for this reaction has not been very successful due to either the over-oxidation to ortho-quinone when using tyrosinases from bacteria or plants, or the lack of the native cofactor, tetrahydrobiopterin (BH4), needed for the activity of tyrosine hydroxylases (TH). Here, we demonstrate that an Escherichia coli cofactor, tetrahydromonapterin (MH4), can be used as an alternative cofactor for TH in presence of the BH4 regeneration pathway, and tyrosine hydroxylation is performed without over-oxidation. We used this platform for biosynthesis of one of the most powerful antioxidants, hydroxytyrosol. An endogenous aromatic aldehyde oxidase was identified and knocked out to prevent formation of the side product, and this resulted in nearly exclusive production of hydroxytyrosol in engineered E. coli. Finally, hydroxytyrosol production from a simple sugar as a sole carbon source was demonstrated. |
| Databáze: | OpenAIRE |
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