Synthetic and Systems Biotechnology (Sep 2022)
Metabolic engineering of Yarrowia lipolytica for scutellarin production
- Yina Wang,
- Xiaonan Liu,
- Bihuan Chen,
- Wei Liu,
- Zhaokuan Guo,
- Xiangyu Liu,
- Xiaoxi Zhu,
- Jiayu Liu,
- Jin Zhang,
- Jing Li,
- Lei Zhang,
- Yadi Gao,
- Guanghui Zhang,
- Yan Wang,
- M. Iqbal Choudhary,
- Shengchao Yang,
- Huifeng Jiang
Affiliations
- Yina Wang
- National and Local Joint Engineering Research Center on Germplasm Innovation and Utilization of Chinese Medicinal Materials in Southwest China, Yunnan Agricultural University, Yunnan, Kunming, 650201, China; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Yunnan, Kunming, 650201, China; Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China
- Xiaonan Liu
- Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China; University of Chinese Academy of Sciences, Beijing, 100049, China; National Center of Technology Innovation for Synthetic Biology, Tianjin, 300308, China; Corresponding author. Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
- Bihuan Chen
- National and Local Joint Engineering Research Center on Germplasm Innovation and Utilization of Chinese Medicinal Materials in Southwest China, Yunnan Agricultural University, Yunnan, Kunming, 650201, China; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Yunnan, Kunming, 650201, China; Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China
- Wei Liu
- Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China; National Center of Technology Innovation for Synthetic Biology, Tianjin, 300308, China; College of Life Science and Technology, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China
- Zhaokuan Guo
- National and Local Joint Engineering Research Center on Germplasm Innovation and Utilization of Chinese Medicinal Materials in Southwest China, Yunnan Agricultural University, Yunnan, Kunming, 650201, China; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Yunnan, Kunming, 650201, China; Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China
- Xiangyu Liu
- National and Local Joint Engineering Research Center on Germplasm Innovation and Utilization of Chinese Medicinal Materials in Southwest China, Yunnan Agricultural University, Yunnan, Kunming, 650201, China; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Yunnan, Kunming, 650201, China
- Xiaoxi Zhu
- Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China; University of Chinese Academy of Sciences, Beijing, 100049, China; National Center of Technology Innovation for Synthetic Biology, Tianjin, 300308, China
- Jiayu Liu
- Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China; National Center of Technology Innovation for Synthetic Biology, Tianjin, 300308, China
- Jin Zhang
- Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China; National Center of Technology Innovation for Synthetic Biology, Tianjin, 300308, China
- Jing Li
- Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China; National Center of Technology Innovation for Synthetic Biology, Tianjin, 300308, China
- Lei Zhang
- Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China; National Center of Technology Innovation for Synthetic Biology, Tianjin, 300308, China; College of Life Science and Technology, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China
- Yadi Gao
- Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China; National Center of Technology Innovation for Synthetic Biology, Tianjin, 300308, China
- Guanghui Zhang
- National and Local Joint Engineering Research Center on Germplasm Innovation and Utilization of Chinese Medicinal Materials in Southwest China, Yunnan Agricultural University, Yunnan, Kunming, 650201, China; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Yunnan, Kunming, 650201, China
- Yan Wang
- H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
- M. Iqbal Choudhary
- H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
- Shengchao Yang
- National and Local Joint Engineering Research Center on Germplasm Innovation and Utilization of Chinese Medicinal Materials in Southwest China, Yunnan Agricultural University, Yunnan, Kunming, 650201, China; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Yunnan, Kunming, 650201, China; Corresponding author. National and Local Joint Engineering Research Center on Germplasm Innovation and Utilization of Chinese Medicinal Materials in Southwest China, Yunnan Agricultural University, Yunnan, Kunming, 650201, China.
- Huifeng Jiang
- Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China; University of Chinese Academy of Sciences, Beijing, 100049, China; National Center of Technology Innovation for Synthetic Biology, Tianjin, 300308, China; Corresponding author. Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
- Journal volume & issue
-
Vol. 7,
no. 3
pp. 958 – 964
Abstract
Scutellarin related drugs have superior therapeutic effects on cerebrovascular and cardiovascular diseases. Here, an optimal biosynthetic pathway for scutellarin was constructed in Yarrowia lipolytica platform due to its excellent metabolic potential. By integrating multi-copies of core genes from different species, the production of scutellarin was increased from 15.11 mg/L to 94.79 mg/L and the ratio of scutellarin to the main by-product was improved about 110-fold in flask condition. Finally, the production of scutellarin was improved 23-fold and reached to 346 mg/L in fed-batch bioreactor, which was the highest reported titer for de novo production of scutellarin in microbes. Our results represent a solid basis for further production of natural products on unconventional yeasts and have a potential of industrial implementation.