Dual pathway for metabolic engineering of E. coli metabolism to produce the highly valuable hydroxytyrosol
Autor: | Filippos Ververidis, Maria Halabalaki, Emmanouil A. Trantas, Theofilos Pavlidis, Theodora Nikou, Eleni Navakoudis, Leandros Skaltsounis |
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Rok vydání: | 2019 |
Předmět: |
2. Zero hunger
0106 biological sciences 0303 health sciences Growth medium Metabolism medicine.disease_cause 01 natural sciences Metabolic engineering 03 medical and health sciences chemistry.chemical_compound Nutraceutical chemistry Biochemistry 010608 biotechnology medicine Hydroxytyrosol Tyrosine Escherichia coli Function (biology) 030304 developmental biology |
Popis: | One of the most abundant phenolic compounds traced in olive tissues is Hydroxytyrosol (HT), a molecule that has been attributed with a pile of beneficial effects, well documented by many epidemiological studies and thus adding value to products containing it. Strong antioxidant capacity and protection from cancer are only some of its exceptional features making it ideal as a potential supplement or preservative to be employed in the nutraceutical, agrochemical, cosmeceutical, and food industry. The HT biosynthetic pathway in plants (e.g. olive fruit tissues) is not well apprehended yet. In this contribution we employed a metabolic engineering strategy by constructing a dual pathway introduced inEscherichia coliand proofing its significant functionality leading it to produce HT. Our primary target was to investigate whether such a metabolic engineering approach could benefit the metabolic flow of tyrosine introduced to the conceived dual pathway, leading to the maximalization of the HT productivity. Various gene combinations derived from plants or bacteria were used to form a newly-inspired, artificial biosynthetic dual pathway managing to redirect the carbon flow towards the production of HT directly from glucose. Various biosynthetic bottlenecks faced due tofeaBgene function, resolved through the overexpression of a functional aldehyde reductase. Currently, we have achieved equimolar concentration of HT to tyrosine as precursor when overproduced straight from glucose, reaching the level of 1.76 mM (270.8 mg/L) analyzed by LC-HRMS. This work realizes the existing bottlenecks of the metabolic engineering process that was dependent on the utilized host strain, growth medium as well as to other factors studied in this work. |
Databáze: | OpenAIRE |
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