Modular co-culture engineering of Yarrowia lipolytica for amorphadiene biosynthesis

Monireh Marsafari, Fidelis Azi, Shaohua Dou*, Peng Xu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Amorphadiene is the precursor to synthesize the antimalarial drug artemisinin. The production of amorphadiene and artemisinin from metabolically engineered microbes may provide an alternate to plant secondary metabolite extraction. Microbial consortia can ofer division of labor, and microbial co-culture system can be leveraged to achieve cost-efcient production of natural products. Using a co-culture system of Y. lipolytica Po1f and Po1g strains, subcellular localization of ADS gene (encoding amorphadiene synthase) into the endoplasmic reticulum, co-utilization of mixed carbon source, and enlargement of the endoplasmic reticulum (ER) surface area, we were able to signifcantly improve amorphadiene production in this work. Using Po1g/PPtM and Po1f/AaADSERx3/iGFMPDU strains and co-utilization of 5 µM sodium acetate with 20 g/L glucose in YPD media, amorphadiene titer were increased to 65.094 mg/L. The enlargement of the ER surface area caused by the deletion of the PAH1 gene provided more subcellular ER space for the action of the ADS-tagged gene. It further increased the amorphadiene production to 71.74 mg/L. The results demonstrated that the importance of the spatial localization of critical enzymes, and manipulating metabolic fux in the co-culture of Y. lipolytica can be efcient over a single culture for the bioproduction of isoprenoid-related secondary metabolites in a modular manner.
Original languageEnglish
JournalMicrobial Cell Factories
DOIs
StateE-pub ahead of print - 31 Dec 2022

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