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
相关论文
共 66 条
[11]   An Efficient Chemical Synthesis of Scutellarein: An in Vivo Metabolite of Scutellarin [J].
Dong, Ze-Xi ;
Li, Nian-Guang ;
Zhang, Peng-Xuan ;
Gu, Ting ;
Wu, Wen-Yu ;
Shi, Zhi-Hao .
MOLECULES, 2016, 21 (03)
[12]   Metabolic engineering of Saccharomyces cerevisiae for de novo production of dihydrochalcones with known antioxidant, antidiabetic, and sweet tasting properties [J].
Eichenberger, Michael ;
Lehka, Beata Joanna ;
Folly, Christophe ;
Fischer, David ;
Martens, Stefan ;
Simon, Ernesto ;
Naesby, Michael .
METABOLIC ENGINEERING, 2017, 39 :80-89
[13]   Characterization of acetyl-CoA synthetase kinetics and ATP-binding [J].
Gallego-Jara, Julia ;
Lozano Terol, Gema ;
Ecija Conesa, Ana ;
Zambelli, Barbara ;
Canvas Diaz, Manuel ;
de Diego Puente, Teresa .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2019, 1863 (06) :1040-1049
[14]   Therapeutic Effects of Breviscapine in Cardiovascular Diseases: A Review [J].
Gao, Jialiang ;
Chen, Guang ;
He, Haoqiang ;
Liu, Chao ;
Xiong, Xingjiang ;
Li, Jun ;
Wang, Jie .
FRONTIERS IN PHARMACOLOGY, 2017, 8
[15]  
Gibson DG, 2009, NAT METHODS, V6, P343, DOI [10.1038/NMETH.1318, 10.1038/nmeth.1318]
[16]   Engineering Yarrowia lipolytica as a Chassis for De Novo Synthesis of Five Aromatic-Derived Natural Products and Chemicals [J].
Gu, Yang ;
Ma, Jingbo ;
Zhu, Yonglian ;
Ding, Xinyu ;
Xu, Peng .
ACS SYNTHETIC BIOLOGY, 2020, 9 (08) :2096-2106
[17]   De novo production of resveratrol from glycerol by engineering different metabolic pathways in Yarrowia lipolytica [J].
He, Qin ;
Szczepanska, Patrycja ;
Yuzbashev, Tigran ;
Lazar, Zbigniew ;
Ledesma-Amaro, Rodrigo .
METABOLIC ENGINEERING COMMUNICATIONS, 2020, 11
[18]   EasyCloneYALI: CRISPR/Cas9-Based Synthetic Toolbox for Engineering of the Yeast Yarrowia lipolytica [J].
Holkenbrink, Carina ;
Dam, Marie I. ;
Kildegaard, Kanchana R. ;
Beder, Johannes ;
Dahlin, Jonathan ;
Belda, David Domenech ;
Borodina, Irina .
BIOTECHNOLOGY JOURNAL, 2018, 13 (09)
[19]   Engineering chimeric diterpene synthases and isoprenoid biosynthetic pathways enables high-level production of miltiradiene in yeast [J].
Hu, Tianyuan ;
Zhou, Jiawei ;
Tong, Yuru ;
Su, Ping ;
Li, Xinlin ;
Liu, Yuan ;
Liu, Nan ;
Wu, Xiaoyi ;
Zhang, Yifeng ;
Wang, Jiadian ;
Gao, Linhui ;
Tu, Lichan ;
Lu, Yun ;
Jiang, Zhouqian ;
Zhou, Yongjin J. ;
Gao, Wei ;
Huang, Luqi .
METABOLIC ENGINEERING, 2020, 60 :87-96
[20]   Improve the Biosynthesis of Baicalein and Scutellarein via Manufacturing Self-Assembly Enzyme Reactor In Vivo [J].
Ji, Dongni ;
Li, Jianhua ;
Xu, Fanglin ;
Ren, Yuhong ;
Wang, Yong .
ACS SYNTHETIC BIOLOGY, 2021, 10 (05) :1087-1094