Biosynthesis and Biotechnological Synthesis of Hydroxytyrosol

Abstract

Hydroxytyrosol (HT), a plant-derived phenolic compound, is recognized for its potent antioxidant capabilities alongside a spectrum of pharmacological benefits, including anti-inflammatory, anti-cancer, anti-bacterial, and anti-viral properties. These attributes have propelled HT into the spotlight as a premier nutraceutical and food additive, heralding a new era in health and wellness applications. Traditional methods for HT production, encompassing physico-chemical techniques and plant extraction, are increasingly being supplanted by biotechnological approaches. These modern methodologies offer several advantages, notably environmental sustainability, safety, and cost-effectiveness, which align with current demands for green and efficient production processes. This review delves into the biosynthetic pathways of HT, highlighting the enzymatic steps involved and the pivotal role of genetic and metabolic engineering in enhancing HT yield. It also surveys the latest progress in the biotechnological synthesis of HT, examining innovative strategies that leverage both genetically modified and non-modified organisms. Furthermore, this review explores the burgeoning potential of HT as a nutraceutical, underscoring its diverse applications and the implications for human health. Through a detailed examination of both the biosynthesis and biotechnological advances in HT production, this review contributes valuable insights to the field, charting a course towards the sustainable and scalable production of this multifaceted compound.

Keywords: industrial applications; nutraceutical; olive leaves; sustainable production; synthetic biology.

Figure 1

Functions of HT.

Figure 2

Production of HT by non-genetically engineered bacteria (adapted from Bouallagui and Sayadi [35], Carlozzi et al. [36], Rebollo-Romero et al. [37], and Anissi et al. [38]).

Figure 3

Pathway for oxidation of tyrosine to HT (adapted from Chen et al. [44]). (a) Highly efficient mutant enzymes HpaBC and TYO were obtained by protein engineering, which sequentially lifted the two rate-limiting steps in the original HT synthesis pathway and increased the HT synthesis capacity of the original synthesis pathway (conversion rate greater than 90%). (b) L-tyrosine oxidation is catalyzed by tyrosine hydroxylase (TH) in the presence of the pterin cofactor (conversion rate less than 20%). DODC: L-DOPA decarboxylase; TYO: tyramine oxidase; ADH: alcohol dehydrogenase; 3,4-DHPAA: 3,4-dihydroxyphenylacetaldehyde.

Figure 4

De novo biosynthesis of HT using a co-culture system consisting of S. cerevisiae and E. coli (adapted from Liu et al. [51]). 4-HPAA: 4-hydroxyphenylacetaldehyde; 4-HPP: 4-hydroxyphenylpyruvic; FAD: flavin adenine dinucleotide; FADH₂: flavin adenine dinucleotide reduced; NADH: nicotinamide adenine dinucleotide.

Figure 5

Applications and perspectives of HT.