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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
PubMed
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.

Keywords:
Mevalonate pathwayMicrobial cell factoryMyrcene biosynthesisNuclear engineeringSubcellular compartmentalization

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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.