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Engineering a Yeast Cell Factory to Sustainably Biosynthesize Parthenolide
Wenping Wei1,2, Chengshuai Yang1, Zhen Su1,2
1CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
ACS Synthetic Biology
|March 6, 2025
Summary
Microbial production of the anticancer compound parthenolide was significantly enhanced using metabolic engineering and a novel metabolic pathway. This sustainable approach achieved record-breaking yields in yeast cell factories.
Area of Science:
- Biotechnology
- Metabolic Engineering
- Natural Product Biosynthesis
Background:
- Parthenolide, a sesquiterpene lactone, shows promise as an anticancer agent.
- Microbial biosynthesis offers a sustainable alternative to plant extraction for parthenolide production.
Purpose of the Study:
- To enhance parthenolide production in microbial cell factories.
- To develop a sustainable and efficient method for producing parthenolide.
Main Methods:
- Metabolic engineering strategies and a novel noncanonical tricarboxylic acid (TCA) cycle were employed.
- Identification of new dehydrogenases and control of parthenolide synthase expression.
- Two-stage fermentation with in situ product extraction using macroreticular resin.
Main Results:
- Enhanced production of the precursor germacrene A.
- Elimination of byproducts and increased parthenolide yield.
- Achieved a parthenolide titer of 549.7 mg/L and costunolide titer of 972.7 mg/L in a 10 L fermenter, the highest reported via microbial fermentation.
Conclusions:
- The developed strategies significantly boosted parthenolide production in yeast.
- This work establishes a high-titer microbial fermentation process for parthenolide.
- The approaches are applicable to the microbial production of other toxic natural products.
