Engineering Yarrowia lipolytica for high-level β-elemene production via combinatorial metabolic strategies
β-Elemene, a pharmacologically active sesquiterpene derived from the traditional Chinese medicinal herb Curcuma wenyujin, exhibits broad-spectrum anti-tumor and anti-inflammatory activities. Currently, its commercial production relies heavily on plant extraction, a process associated with high costs...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2025-12-01
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| Series: | Synthetic and Systems Biotechnology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X25000924 |
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| Summary: | β-Elemene, a pharmacologically active sesquiterpene derived from the traditional Chinese medicinal herb Curcuma wenyujin, exhibits broad-spectrum anti-tumor and anti-inflammatory activities. Currently, its commercial production relies heavily on plant extraction, a process associated with high costs and environmental burdens, limiting industrial scalability. To address these challenges, we developed a metabolically engineered Yarrowia lipolytica strain as an efficient microbial cell factory for de novo Germacrene A biosynthesis, the direct precursor of β-elemene. Through combinatorial optimization strategies—including (1) mevalonate (MVA) pathway enhancement, (2) copy number amplification of germacrene A synthase (GAS), (3) β-oxidation pathway reinforcement, and (4) introduction of the isopentenyl utilization pathway (IUP)—we significantly improved β-elemene production. The engineered strain achieved a titer of 3.08 ± 0.05 g/L in shake-flask cultures, with a yield of 51.27 ± 0.75 mg/g glucose, representing a 3.5-fold increase over the parental strain. Our work highlights the potential of Y. lipolytica as a sustainable and scalable platform for high-value sesquiterpene production, offering a viable alternative to plant-derived extraction. |
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| ISSN: | 2405-805X |