Construction of <i>Saccharomyces cerevisiae</i> 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 <i>Saccharomyces cerevisiae</i> 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 <i>S. cerevisiae</i> 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.