Efficient production of astaxanthin in Yarrowia lipolytica through metabolic and enzyme engineering
Astaxanthin is a natural red carotenoid, commonly used as an additive in the pharmaceutical industry and as a nutritional supplement owing to its notable antioxidant benefits. However, a complex biosynthetic pathway poses a challenge to de novo biosynthesis of astaxanthin. Here, Yarrowia lipolytica...
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| Veröffentlicht in: | Synthetic and systems biotechnology Jg. 10; H. 3; S. 737 - 750 |
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| Hauptverfasser: | , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
China
Elsevier B.V
01.09.2025
KeAi Publishing Communications Ltd KeAi Publishing KeAi Communications Co., Ltd |
| Schlagworte: | |
| ISSN: | 2405-805X, 2405-805X |
| Online-Zugang: | Volltext |
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| Zusammenfassung: | Astaxanthin is a natural red carotenoid, commonly used as an additive in the pharmaceutical industry and as a nutritional supplement owing to its notable antioxidant benefits. However, a complex biosynthetic pathway poses a challenge to de novo biosynthesis of astaxanthin. Here, Yarrowia lipolytica was engineered through multiple strategies for high level production of astaxanthin using a cheap mineral medium. For the production of β-carotene, a platform strain was constructed in which 411.7 mg/L of β-carotene was produced at a shake-flask level. Integration of algal β-carotene ketolase and β-carotene hydroxylase led to the production of 12.3 mg/L of astaxanthin. Furthermore, construction of HpBKT and HpCrtZ as a single enzyme complex along with the enhanced catalytic activity of the enzymes led to the accumulation of 41.0 mg/L of astaxanthin. Iterative gene integration into the genome and direction of the astaxanthin production pathway into sub-organelles substantially increased astaxanthin production (172.1 mg/L). Finally, restoration of the auxotrophic markers and medium optimization further improved astaxanthin production to 237.3 mg/L. The aforementioned approaches were employed in fed-batch fermentation to produce 2820 mg/L of astaxanthin (229-fold improvement regarding the starter strain), with an average productivity of 434 mg/L/d and a yield of 5.6 mg/g glucose, which is the highest reported productivity in Y. lipolytica.
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| Bibliographie: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ISSN: | 2405-805X 2405-805X |
| DOI: | 10.1016/j.synbio.2025.02.014 |