Abstract
Tyrosol is extensively used in the pharmaceutical industry as an important natural product from plants. In this study, an exogenous pathway involved in catalyzing tyrosine to tyrosol was introduced into Saccharomyces cerevisiae. Furthermore, The pyruvate decarboxylase gene pdc1 was deleted to redirect the flux distribution at the pyruvate node, and a bifunctional NAD+-dependent fused chorismate mutase/prephenate dehydrogenase from E. coli (EcTyrA) and its' tyrosine inhibition resistant mutant (EcTyrAM53I/A354V) were heterologously expression in S. cerevisiae to tuning up the chorismate metabolism effectively directed the metabolic flux toward tyrosol production. Finally, the tyrosol yield of the engineered strain GFT-4 was improved to 126.74 ± 6.70 mg/g DCW at 48 h, increased 440 times compared with that of the control strain GFT-0 (0.28 ± 0.01 mg/g DCW). The new synergetic engineering strategy developed in this study can be further applied to increase the production of high value-added aromatic compounds derived from aromatic amino acid or shikimate in S. cerevisiae.
Highlights
Tyrosol is a phenethyl alcohol derivative known to have antioxidant and anti-inflammatory effects (Kim et al, 2017)
There was no significant change in biomass among strains GFT-2, GFT-3, and GFT-4 (Figure 2). These results suggested that heterologously expressing EcTyrA or EcTyrAM53I/A354V in S. cerevisiae could enhance the upstream of chorismate metabolism and improve the tyrosol production
We modified three modules involved in tyrosol biosynthesis to effectively improve the tyrosol production of S. cerevisiae (Figure 1)
Summary
Tyrosol is a phenethyl alcohol derivative known to have antioxidant and anti-inflammatory effects (Kim et al, 2017). Tyrosol is an important pharmaceutical intermediate and can be used as a precursor of salidroside (Ma et al, 2012), icariside D2 (Liao et al, 2018; Torrens-Spence et al, 2018), and hydroxytyrosol (Allouche and Sayadi, 2005; Li et al, 2018) in the pharmaceutical industry. These drugs have activities against cardiovascular disease (Granados-Principal et al, 2010; Hu et al, 2014), cancer (Hu et al, 2010; Liu et al, 2012), and viruses (Wang et al, 2009). The biosynthesis of tyrosol has received increasing
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