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ACS Synth Biol. 2019 Apr 19;8(4):724-733. doi: 10.1021/acssynbio.8b00360. Epub 2019 Feb 28.

Constructing Yeast Chimeric Pathways To Boost Lipophilic Terpene Synthesis.

Liu D1,2, Liu H1,2, Qi H1,2, Guo XJ1,2, Jia B1,2, Zhang JL1,2, Yuan YJ1,2.

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Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology , Tianjin University , Tianjin 300350 , P. R. China.
SynBio Research Platform , Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300072 , PR China.


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.


DNA assembly; Saccharomyces cerevisiae; Yarrowia lipolytica; synthetic biology; terpene; transcriptional unit


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