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Enhancing myrcene biosynthesis in yeast through nuclear compartmentalization.
Zihan Wang1,2, Jing Wang1,3, Yanhui Liu4
1School of Agriculture and Biotechnology, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, 518107, China.
Synthetic and Systems Biotechnology
|July 2, 2026
Summary
Engineering the yeast nucleus for myrcene biosynthesis significantly boosted production. This compartmentalization strategy overcomes metabolic flux limitations, achieving high titers of this valuable monoterpene.
Area of Science:
- Synthetic Biology
- Metabolic Engineering
- Biotechnology
Background:
- Myrcene is a valuable monoterpene with applications in fragrance, flavor, and agriculture.
- Efficient microbial production of myrcene is hindered by pathway competition and limited metabolic flux.
- Compartmentalization in Saccharomyces cerevisiae offers a strategy to spatially organize metabolic pathways, improving efficiency.
Purpose of the Study:
- To engineer the yeast nucleus as a synthetic metabolic compartment for myrcene biosynthesis.
- To enhance metabolic flux and overcome limitations in microbial myrcene production.
Main Methods:
- Engineered the Saccharomyces cerevisiae nucleus for myrcene biosynthesis.
- Screened myrcene synthases from Snapdragon Oc15 and Picea abies.
- Co-localized myrcene synthase and GPP synthase (mERG20p) to the nucleus.
- Reconstructed the mevalonate (MVA) pathway within the nucleus.
- Optimized rate-limiting steps to enhance metabolic flux.
Main Results:
- Myrcene production was detected only upon co-localization of myrcene synthase and mERG20p to the nucleus.
- Cytosolic co-expression failed to yield detectable myrcene.
- Nuclear reconstruction of the MVA pathway increased myrcene titers.
- Achieved a final myrcene titer of 23.4 mg/L in flask-shaking fermentation.
Conclusions:
- Demonstrated the feasibility of repurposing the yeast nucleus for efficient myrcene biosynthesis.
- Established a novel strategy for improving microbial production of myrcene through nuclear compartmentalization.
- The engineered nucleus effectively separated myrcene biosynthesis from competing cytosolic metabolism.
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