De novo biosynthesis of quercetin in Yarrowia Lipolytica through systematic metabolic engineering for enhanced yield
Abstract Kaempferol and quercetin possess various biological activities, making them valuable in food and medicine. However, their production via traditional methods is often inefficient. This study aims to address this gap by engineering the yeast Yarrowia lipolytica to achieve high yields of these...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-01-01
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| Series: | Bioresources and Bioprocessing |
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| Online Access: | https://doi.org/10.1186/s40643-024-00825-w |
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| author | Yuxing Dong Wenping Wei Mengfan Li Tao Qian Jiayun Xu Xiaohe Chu Bang-Ce Ye |
| author_facet | Yuxing Dong Wenping Wei Mengfan Li Tao Qian Jiayun Xu Xiaohe Chu Bang-Ce Ye |
| author_sort | Yuxing Dong |
| collection | DOAJ |
| description | Abstract Kaempferol and quercetin possess various biological activities, making them valuable in food and medicine. However, their production via traditional methods is often inefficient. This study aims to address this gap by engineering the yeast Yarrowia lipolytica to achieve high yields of these flavonoids. We designed a kaempferol biosynthetic pathway by integrating multiple-copy fusion enzyme expression modules, F3H-(GGGGS)2-FLS, into the genome with an optimized linker (GGGGS)2 to enhance kaempferol production from naringenin. To synthesize quercetin de novo, we introduced the FMOCPR gene into the kaempferol-synthesizing strain using the optimized pFBAin promoter. Notably, increasing glucose concentration effectively boosted the production of both flavonoids. Our results demonstrated kaempferol and quercetin titers reaching 194.30 ± 7.69 and 278.92 ± 11.58 mg/L, respectively, in shake-flask cultures. These findings suggest that Y. lipolytica is a promising platform for the efficient production of flavonoid-derived products. |
| format | Article |
| id | doaj-art-07f9daf94cc440a7a7ddb83344bf852b |
| institution | Kabale University |
| issn | 2197-4365 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Bioresources and Bioprocessing |
| spelling | doaj-art-07f9daf94cc440a7a7ddb83344bf852b2025-01-26T12:12:34ZengSpringerOpenBioresources and Bioprocessing2197-43652025-01-0112111010.1186/s40643-024-00825-wDe novo biosynthesis of quercetin in Yarrowia Lipolytica through systematic metabolic engineering for enhanced yieldYuxing Dong0Wenping Wei1Mengfan Li2Tao Qian3Jiayun Xu4Xiaohe Chu5Bang-Ce Ye6Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of TechnologyInstitute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of TechnologyInstitute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of TechnologyInstitute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of TechnologyInstitute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of TechnologyInstitute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of TechnologyInstitute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of TechnologyAbstract Kaempferol and quercetin possess various biological activities, making them valuable in food and medicine. However, their production via traditional methods is often inefficient. This study aims to address this gap by engineering the yeast Yarrowia lipolytica to achieve high yields of these flavonoids. We designed a kaempferol biosynthetic pathway by integrating multiple-copy fusion enzyme expression modules, F3H-(GGGGS)2-FLS, into the genome with an optimized linker (GGGGS)2 to enhance kaempferol production from naringenin. To synthesize quercetin de novo, we introduced the FMOCPR gene into the kaempferol-synthesizing strain using the optimized pFBAin promoter. Notably, increasing glucose concentration effectively boosted the production of both flavonoids. Our results demonstrated kaempferol and quercetin titers reaching 194.30 ± 7.69 and 278.92 ± 11.58 mg/L, respectively, in shake-flask cultures. These findings suggest that Y. lipolytica is a promising platform for the efficient production of flavonoid-derived products.https://doi.org/10.1186/s40643-024-00825-wBiosynthesisYarrowia LipolyticaKaempferolQuercetinMetabolic engineering |
| spellingShingle | Yuxing Dong Wenping Wei Mengfan Li Tao Qian Jiayun Xu Xiaohe Chu Bang-Ce Ye De novo biosynthesis of quercetin in Yarrowia Lipolytica through systematic metabolic engineering for enhanced yield Bioresources and Bioprocessing Biosynthesis Yarrowia Lipolytica Kaempferol Quercetin Metabolic engineering |
| title | De novo biosynthesis of quercetin in Yarrowia Lipolytica through systematic metabolic engineering for enhanced yield |
| title_full | De novo biosynthesis of quercetin in Yarrowia Lipolytica through systematic metabolic engineering for enhanced yield |
| title_fullStr | De novo biosynthesis of quercetin in Yarrowia Lipolytica through systematic metabolic engineering for enhanced yield |
| title_full_unstemmed | De novo biosynthesis of quercetin in Yarrowia Lipolytica through systematic metabolic engineering for enhanced yield |
| title_short | De novo biosynthesis of quercetin in Yarrowia Lipolytica through systematic metabolic engineering for enhanced yield |
| title_sort | de novo biosynthesis of quercetin in yarrowia lipolytica through systematic metabolic engineering for enhanced yield |
| topic | Biosynthesis Yarrowia Lipolytica Kaempferol Quercetin Metabolic engineering |
| url | https://doi.org/10.1186/s40643-024-00825-w |
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