Systematic metabolic engineering of Yarrowia lipolytica for efficient production of phytohormone abscisic acid
Abscisic acid (ABA) is an important phytohormone with diverse applications. It currently relies on the fermentation of Botrytis cinerea, which suffers from limited availability of genetic engineering tools. Here, Yarrowia lipolytica was engineered to enable de novo biosynthesis of ABA. To overcome t...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2025-03-01
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| Series: | Synthetic and Systems Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X24001340 |
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| author | Mei-Li Sun Ziyun Zou Lu Lin Rodrigo Ledesma-Amaro Kaifeng Wang Xiao-Jun Ji |
| author_facet | Mei-Li Sun Ziyun Zou Lu Lin Rodrigo Ledesma-Amaro Kaifeng Wang Xiao-Jun Ji |
| author_sort | Mei-Li Sun |
| collection | DOAJ |
| description | Abscisic acid (ABA) is an important phytohormone with diverse applications. It currently relies on the fermentation of Botrytis cinerea, which suffers from limited availability of genetic engineering tools. Here, Yarrowia lipolytica was engineered to enable de novo biosynthesis of ABA. To overcome the rate-limiting P450 enzymes, systematic engineering strategies were implemented. Firstly, the dissolved oxygen was increased to boost the activity of P450 enzymes. Secondly, the expansion of endoplasmic reticulum was implemented to improve the functional expression of P450 enzymes. Lastly, rate-limiting enzymes were assembled to facilitate substrate trafficking. Moreover, ABA production was further improved by strengthening the mevalonate pathway. Finally, the engineered strain produced 1221.45 mg/L of ABA in a 5-L bioreactor. The study provides effective approaches for alleviating rate-limiting P450 enzymes to enhance ABA production and achieve competitive industrial-level ABA production in Y. lipolytica. |
| format | Article |
| id | doaj-art-2b30b78b8bfb4ecf82b50f9fe4d160b9 |
| institution | DOAJ |
| issn | 2405-805X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Synthetic and Systems Biotechnology |
| spelling | doaj-art-2b30b78b8bfb4ecf82b50f9fe4d160b92025-08-20T03:13:21ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2025-03-0110116517310.1016/j.synbio.2024.10.004Systematic metabolic engineering of Yarrowia lipolytica for efficient production of phytohormone abscisic acidMei-Li Sun0Ziyun Zou1Lu Lin2Rodrigo Ledesma-Amaro3Kaifeng Wang4Xiao-Jun Ji5State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing, 211816, People's Republic of ChinaState Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing, 211816, People's Republic of ChinaState Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing, 211816, People's Republic of ChinaDepartment of Bioengineering and Imperial College Centre for Synthetic Biology, Imperial College London, London, SW7 2AZ, United KingdomState Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing, 211816, People's Republic of China; Corresponding author.State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing, 211816, People's Republic of China; Corresponding author.Abscisic acid (ABA) is an important phytohormone with diverse applications. It currently relies on the fermentation of Botrytis cinerea, which suffers from limited availability of genetic engineering tools. Here, Yarrowia lipolytica was engineered to enable de novo biosynthesis of ABA. To overcome the rate-limiting P450 enzymes, systematic engineering strategies were implemented. Firstly, the dissolved oxygen was increased to boost the activity of P450 enzymes. Secondly, the expansion of endoplasmic reticulum was implemented to improve the functional expression of P450 enzymes. Lastly, rate-limiting enzymes were assembled to facilitate substrate trafficking. Moreover, ABA production was further improved by strengthening the mevalonate pathway. Finally, the engineered strain produced 1221.45 mg/L of ABA in a 5-L bioreactor. The study provides effective approaches for alleviating rate-limiting P450 enzymes to enhance ABA production and achieve competitive industrial-level ABA production in Y. lipolytica.http://www.sciencedirect.com/science/article/pii/S2405805X24001340Abscisic acidPhytohormoneSesquiterpeneYarrowia lipolyticaP450 enzymes |
| spellingShingle | Mei-Li Sun Ziyun Zou Lu Lin Rodrigo Ledesma-Amaro Kaifeng Wang Xiao-Jun Ji Systematic metabolic engineering of Yarrowia lipolytica for efficient production of phytohormone abscisic acid Synthetic and Systems Biotechnology Abscisic acid Phytohormone Sesquiterpene Yarrowia lipolytica P450 enzymes |
| title | Systematic metabolic engineering of Yarrowia lipolytica for efficient production of phytohormone abscisic acid |
| title_full | Systematic metabolic engineering of Yarrowia lipolytica for efficient production of phytohormone abscisic acid |
| title_fullStr | Systematic metabolic engineering of Yarrowia lipolytica for efficient production of phytohormone abscisic acid |
| title_full_unstemmed | Systematic metabolic engineering of Yarrowia lipolytica for efficient production of phytohormone abscisic acid |
| title_short | Systematic metabolic engineering of Yarrowia lipolytica for efficient production of phytohormone abscisic acid |
| title_sort | systematic metabolic engineering of yarrowia lipolytica for efficient production of phytohormone abscisic acid |
| topic | Abscisic acid Phytohormone Sesquiterpene Yarrowia lipolytica P450 enzymes |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X24001340 |
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