De novo biosynthesis of tyrosol acetate and hydroxytyrosol acetate from glucose in engineered Escherichia coli

Abstract

Background: Tyrosol and hydroxytyrosol derived from virgin olive oil and olives extract, have wide applications both as functional food components and as nutraceuticals. However, they have low bioavailability due to their low absorption and high metabolism in human liver and small intestine.Acetylation of tyrosol and hydroxytyrosol can effectively improve their bioavailability and thus increase their potential use in the food and cosmeceutical industries. There is no report on the bioproductin of tyrosol acetate and hydroxytyrosol acetate so far. Thus, it is of great signi cance to develop microbial cell factories for achieving tyrosol acetate or hydroxytyrosol acetate biosynthesis.Results: In this study, two de novo biosynthetic pathways for the production of tyrosol acetate and hydroxytyrosol acetate were constructed in Escherichia coli. First, an engineered E. coli that allows production of tyrosol from simple carbon sources was established. Four aldehyde reductases were compared, and it was found that yeaE is the best aldehyde reductase for tyrosol accumulation. Subsequently, the pathway was extended for tyrosol acetate production by further overexpression of alcohol acetyltransferase ATF1 for the conversion of tyrosol to tyrosol acetate. Finally, the pathway was further extended for hydroxytyrosol acetate production by overexpression of 4-hydroxyphenylacetate 3hydroxylase HpaBC. Conclusion:We have successfully established the arti cial biosynthetic pathway of tyrosol acetate and hydroxytyrosol acetate from fermentable sugars and demonstrated for the rst time the direct fermentative production of tyrosol acetate and hydroxytyrosol acetate from glucose in engineered E. coli

Promoting FADH2 Regeneration of Hydroxylation for High-Level Production of Hydroxytyrosol from Glycerol in Escherichia coli

“…In conclusion, the highest hydroxytyrosol production to date has been achieved with the addition of glycerol through modifications of the carbon metabolic pathway, cofactor engineering, and fermentation optimization. In fact, in recent years, there have also been many studies related to the upstream and downstream products of hydroxytyrosol, such as tyrosol and hydroxytyrosol acetate. , The present study provides a strategy for the biosynthesis of other similar substances and lays the foundation for the biosynthesis of downstream substances such as verbascoside . However, there are still many strategies to be explored, and the supply of precursors needs to be further strengthened.…”

De Novo Biosynthesis of 4-Vinylanisole in Engineered Escherichia coli

“…The plasmid pDG20 with the coexpression of feedback-resistant chorismate mutase/prephenate dehydrogenase ( tyrA fbr ) and 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase ( aroG fbr ) and pST04 with the coexpression of PEP synthase ( ppsA ) and transketolase I ( tktA ) were constructed in our previous studies. , The XbaI- Sal I fragment of aroG fbr and tyrA fbr from pDG20 was inserted into XbaI and Sal I sites of pBBRMCS1 to give pHG05. The XbaI-XhoI fragment of ppsA and tktA from pST04 was inserted into XbaI and XhoI sites of pET28b-pSC101 to give pHG06.…”

Advances in 4-Hydroxyphenylacetate-3-hydroxylase Monooxygenase

“…HpaBC catalyzes the hydroxylation of the generated tyrosol to hydroxytyrosol and ATF1, which catalyzes the acetylation of hydroxytyrosol to hydroxytyrosol acetate. The engineered E. coli could produce 225.0 mg·L −1 hydroxytyrosol acetate from glucose within 28 h [ 60 ]. This study represents a promising alternative to producing hydroxytyrosol acetate from renewable resources.…”

“…The results indicate the promising and sustainable production of hydroxytyrosol and show a wide potential. Guo et al produced hydroxytyrosol acetate from glucose by overexpressing HpaBC from E. coli and alcohol acetyltransferase (ATF1) from S. cerevisiae in a tyrosol-producing E. coli strain [60] (Figure 10). HpaBC catalyzes the hydroxylation of the generated tyrosol to hydroxytyrosol and ATF1, which catalyzes the acetylation of hydroxytyrosol to hydroxy-tyrosol acetate.…”