Construction of Saccharomyces cerevisiae Platform Strain for the Biosynthesis of Carotenoids and Apocarotenoids

Carotenoids and apocarotenoids, natural compounds with vital biological functions, are now sustainably produced via microbial synthesis as an eco-friendly alternative to inefficient and polluting traditional plant-based extraction methods. In their biosynthesis, β-carotene (BC) plays a crucial role as it is the key intermediate from which different downstream derivatives are formed. Here, we engineered a high-producing Saccharomyces cerevisiae platform strain to produce BC through a combination of systematic metabolic engineering and atmospheric and room temperature plasma mutagenesis. The strain achieved a BC production of 2.09 g/L via fed-batch fermentation in a 5-L bioreactor, the highest yield reported in S. cerevisiae to date. Using this platform strain, we constructed zeaxanthin- and β-ionone-producing strains by introducing key enzyme genes. The engineered strains produced 39.09 mg/L of zeaxanthin and 31.87 mg/L of β-ionone in shake-flask cultures. The engineered BC platform established in this study provides a higher starting point for producing diverse BC derivatives.