Hydroxytyrosol (HT) is a natural antioxidant widely employed in the food production, pharmaceutical, and cosmetic industries. Microbial fermentation for HT production holds significant potential for industrial applications. In this study, we constructed and optimized a biosynthetic pathway for HT in Yarrowia lipolytica for the first time. Initially, HT biosynthesis was achieved by introducing hpaBC, along with ARO10 and ADH6 from Saccharomyces cerevisiae . By employing strategies such as relieving feedback inhibition in the shikimate pathway, optimizing cofactor supply, weakening competing pathways, and balancing metabolic flux, the HT titer was elevated to 2438.27 mg/L. Finally, the engineered strain HT43 produced 11.9 g/L of HT in a 1.3 L bioreactor, which was 917.5 times higher than the initial level. This work sets a new record for the de novo production of HT in a microbial host, achieving the highest titer reported to date, and it offers a novel fermentation strategy with potential for industrial HT production.
Liu et al. (Sat,) studied this question.