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

doi:10.1016/j.synbio.2022.05.009

Metabolic engineering of Yarrowia lipolytica for scutellarin production

Synth Syst Biotechnol. 2022 Jun 6;7(3):958-964. doi: 10.1016/j.synbio.2022.05.009. eCollection 2022 Sep.

Authors

Yina Wang^{1

2

3}, Xiaonan Liu^{3

4

5}, Bihuan Chen^{1

2

3}, Wei Liu^{3

5

6}, Zhaokuan Guo^{1

2

3}, Xiangyu Liu^{1

2}, Xiaoxi Zhu^{3

4

5}, Jiayu Liu^{3

5}, Jin Zhang^{3

5}, Jing Li^{3

5}, Lei Zhang^{3

5

6}, Yadi Gao^{3

5}, Guanghui Zhang^{1

2}, Yan Wang⁷, M Iqbal Choudhary⁷, Shengchao Yang^{1

2}, Huifeng Jiang^{3

4

5}

Affiliations

¹ 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.
² State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Yunnan, Kunming, 650201, China.
³ Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
⁴ University of Chinese Academy of Sciences, Beijing, 100049, China.
⁵ National Center of Technology Innovation for Synthetic Biology, Tianjin, 300308, China.
⁶ College of Life Science and Technology, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China.
⁷ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.

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.

Keywords: Combinatorial gene overexpression; Metabolic engineering; Scutellarin; Yarrowia lipolytica.