Metabolic engineering of Yarrowia lipolytica for scutellarin production

被引:17
作者
Wang, Yina [1 ,2 ]
Liu, Xiaonan [3 ,4 ,5 ]
Chen, Bihuan [1 ,2 ,3 ]
Liu, Wei [3 ,5 ,6 ]
Guo, Zhaokuan [1 ,2 ,3 ]
Liu, Xiangyu [1 ,2 ]
Zhu, Xiaoxi [3 ,4 ,5 ]
Liu, Jiayu [3 ,5 ]
Zhang, Jin [3 ,5 ]
Li, Jing [3 ,5 ]
Zhang, Lei [3 ,5 ,6 ]
Gao, Yadi [3 ,5 ]
Zhang, Guanghui [1 ,2 ]
Wang, Yan [7 ]
Choudhary, M. Iqbal [7 ]
Yang, Shengchao [1 ,2 ]
Jiang, Huifeng [3 ,4 ,5 ]
机构
[1] Yunnan Agr Univ, Natl & Local Joint Engn Res Ctr Germplasm Innovat, Kunming 650201, Yunnan, Peoples R China
[2] Yunnan Agr Univ, State Key Lab Conservat & Utilizat Bioresources Yu, Kunming 650201, Yunnan, Peoples R China
[3] Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Key Lab Syst Microbial Biotechnol, Tianjin 300308, Peoples R China
[4] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[5] Natl Ctr Technol Innovat Synthet Biol, Tianjin 300308, Peoples R China
[6] Wuhan Polytech Univ, Coll Life Sci & Technol, Wuhan 430023, Hubei, Peoples R China
[7] Univ Karachi, H E J Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan
基金
中国国家自然科学基金;
关键词
Scutellarin; Yarrowialipolytica; Metabolicengineering; Combinatorial gene over expression; DE-NOVO PRODUCTION; SACCHAROMYCES-CEREVISIAE; BIOSYNTHESIS; PATHWAY; BIOAVAILABILITY; OVERPRODUCTION; RESVERATROL; IMPROVE; GLUCOSE; DESIGN;
D O I
10.1016/j.synbio.2022.05.009
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 un-conventional yeasts and have a potential of industrial implementation.
引用
收藏
页码:958 / 964
页数:7
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