De novo biosynthesis of zeaxanthin and 3-hydroxy-β-ionone by engineered Yarrowia lipolytica

Abstract

The yeast Yarrowia lipolytica is an attractive cell factory for the heterologous production of a variety of carotenoids, including lycopene, ꞵ-carotene, and astaxanthin, due to its oleaginous status and high intercellular acetyl-CoA flux. In this study, we engineered the ꞵ-carotene-producing Y. lipolytica strain following multi-level strategies for the efficient accumulation of zeaxanthin, and 3-hydroxy-ꞵ-ionone from its descendant. The most productive pathway combining fermentation optimization, conferred a production titer of 2.55 g/L of zeaxanthin. Furthermore, through screening carotenoid cleavage dioxygenases (CCDs), we showed the discovery and identification of the efficient pathway for conversion of zeaxanthin to 3-hydroxy-ꞵ-ionone (1.66 g/L). This is the first report for the de novo biosynthesis of secreting 3-hydroxy-ꞵ-ionone from a recombinant organism. These results show a significant step towards demonstrating the feasibility of industrial production of biologically-derived carotenoids and apocarotenoids of high value.