ArticleMicrobial cell factories2025
Combinatorial metabolic engineering of Yarrowia lipolytica for high-level production of the plant-derived diterpenoid sclareol.
Article in Microbial cell factories, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed.
- Constructing an efficient synthesis pathway in peroxisomes to boostSynthetic and systems biotechnology · 2026Article
- Review
- Spatial Engineering of Yarrowia lipolytica for the Biosynthesis of Capsanthin.Biotechnology journal · 2026Article
- Metabolic engineering strategies: utilizing different microbial strains and advanced technologies for the synthesis of high-valued terpenoids.Antonie van Leeuwenhoek · 2026Review
- Engineered microorganisms unlock a new era of diterpenoid biomanufacturing: recent advances and future perspectives.Bioresources and bioprocessing · 2026Review
- Synthetic Biology of Sclareol: From the Plant Biosynthetic Pathway to Engineered Microbial and Photosynthetic Chassis.Biotechnology journal · 2026Review
- Directed screening and spatial coupling of farnesyl diphosphate synthase for enhancing menaquinone-7 production in Bacillus subtilis.Microbial cell factories · 2026Article
- Review
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4 authors.
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Abstract
backgroundSclareol, a diterpene alcohol derived from Salvia sclarea, is primarily used in the synthesis of ambrox, an alternative to the expensive spice ambergris. However, commercial production of sclareol from plant extraction is costly and environmentally problematic, limiting its scalability. Recent advances in synthetic biology have enabled the construction of efficient cell factories for sclareol synthesis, offering a more sustainable solution.
resultsIn this study, we engineered Yarrowia lipolytica to produce sclareol by integrating genes encoding (13E)-8α-hydroxylabden-15-yl diphosphate synthase (LPPS) and sclareol synthase (SCS). Sclareol titers were further enhanced through the fusion of SsSCS and SsLPPS proteins, as well as multi-copy gene integration. To increase the precursor geranylgeranyl diphosphate (GGPP), we overexpressed various geranylgeranyl diphosphate synthases (GGS1), resulting in significant accumulation of GGPP. Additionally, optimization of the mevalonate pathway, coupled with the downregulation of lipid synthesis and upregulation of lipid degradation, directed more acetyl CoA towards sclareol production.
conclusionsIn this study, we reprogrammed the metabolism of Y. lipolytica by combinatorial metabolic engineering with a sclareol titer of 2656.20 ± 91.30 mg/L in shake flasks. Our findings provide a viable strategy for utilizing Y. lipolytica as a microbial cell factory to produce sclareol.
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