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Metabolic engineering of Yarrowia lipolytica for scutellarin production

查看全文 作  者:Yina [1,2,3]Wang;Xiaonan [3,4,5]Liu;Bihuan [1,2,3]Chen;Wei [3,5,6]Liu;Zhaokuan [1,2,3]Guo;Xiangyu [1,2]Liu;Xiaoxi [3,4,5]Zhu;Jiayu [3,5]Liu;Jin [3,5]Zhang;Jing [3,5]Li;Lei [3,5,6]Zhang;Yadi [3,5]Gao;Guanghui [1,2]Zhang;Yan [7]Wang;MIqbal [7]Choudhary;Shengchao [1,2]Yang;Huifeng [3,4,5]Jiang 高影响力作者 机构地区:[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高影响力机构 出  处:《Synthetic and Systems Biotechnology》索引2022年第7卷第3期,共7页高影响力期刊 基  金:funding from the Major Science and Technique Programs in Yunnan Province(No.2019ZF011-1);the National Natural Science Foundation of China(No.81960689);the National Key R&D Program of China(2020YFC1316400);the Project of Young and Middle-Aged Talent of Yunnan Province(No.2019HB019);Science and Technology Innovation team of Yunnan(No.202105AE160011);Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(No.TSBICIP-KJGG-002-02);the Tianjin Science Fund for Distinguished Young Scholars(No.18JCJQJC48300). 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 unconventional yeasts and have a potential of industrial implementation. 关 键 词:SCUTELLARIN Yarrowia lipolytica Metabolic engineering Combinatorial gene overexpression
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