Constructing Yeast Chimeric Pathways To Boost Lipophilic Terpene Synthesis

Synthetic chimeric biological system offers opportunities to illuminate principles of designing life, and a primary step is constructing synthetic chimeric pathways. Here, we constructed yeast chimeric pathways by transferring the genes from Saccharomyces cerevisiae pathways into another budding yeast Yarrowia lipolytica for in vivo assembly. We efficiently diversified gene option, combination, localization order, and copy number as expected. Convergence of two yeast pathways, especially mevalonic acid (MVA) pathways, remarkably enhanced synthesis of a lipophilic terpene, lycopene. In the selected champion strain with 50-fold of enhanced lycopene production, the chimeric MVA pathway gathered three S. cerevisiae genes with particular copies and locations. Amazingly, therein we discovered distinct transcriptional up-regulation of three significant pathways correlated with acetyl-CoA supply and tuning of cellular lipid amounts and composition. Modulating these pathways further improved lycopene production to 150-fold, a final 259 mg/L (approximately 80 mg/g DCW). We primarily showed the capacity of boosting the synthesis of lipophilic products with yeast chimeric pathways.