Orchestrating multiple subcellular organelles of Saccharomyces cerevisiae for efficient production of squalene.

Summary

By combinatorially engineering mitochondria, ER, lipid droplets, and the cell wall in S. cerevisiae, the authors increased squalene productivity 3.4-fold over a prior chassis and achieved 55.8 g/L with 0.5 g/L/h productivity. Optimizing NADPH supply provided an additional 3.9% gain, enabling sustainable, animal-free squalene production for cosmetics and other sectors.

Key Findings

• Combinatorial organelle engineering (mitochondria, ER, LDs, CW) boosted squalene productivity 3.4× versus SquMC13.
• Optimizing NADPH generation yielded an additional 3.9% increase in squalene production.
• Achieved titer 55.8 g/L with 0.5 g/L/h productivity and 0.5 g/g dry cell weight specific production.

Clinical Implications

While not clinical, it enables a sustainable, scalable source of squalene (and derivative squalane) for dermatologic and cosmetic formulations, reducing reliance on animal-derived sources.

Limitations

• No pilot-scale fermentation or downstream purification cost analysis presented.
• Environmental life-cycle assessment and regulatory considerations were not reported.

Future Directions

Validate at pilot/commercial scale, perform LCA and techno-economics, evaluate conversion to squalane, and assess stability/quality for cosmetic-grade supply.