生物学杂志

生物学杂志 ›› 2026, Vol. 43 ›› Issue (1): 39-.doi: 10.3969/j.issn.2095-1736.2026.01.039

• 研究报告 • 上一篇    下一篇

代谢工程改造解脂耶氏酵母高效合成角鲨烯

潘雨晴1， 周　菡1， 王　翀1， 杨晓娜1， 段希宇1， 何岳东1， 田　云1,2， 刘虎虎1
  

  1. 1. 湖南农业大学 生物科学技术学院， 长沙 410128； 2. 湖南甜蔓生物科技有限公司， 永州 425900
  • 出版日期:2026-02-18 发布日期:2026-02-27
  • 通讯作者: 田云，博士，教授，研究方向为合成生物学与代谢工程，E-mail：tianyun@hunau.edu.cn；刘虎虎，博士，副教授，研究方向为合成生物学与代谢工程，E-mail：liuhuhu@hunau.edu.cn；田云和刘虎虎为共同通信作者
  • 作者简介:潘雨晴，硕士，研究方向为生物化学与分子生物学，E-mail：PanYQ@stu.hunau.edu.cn
  • 基金资助:
    湖南省科技人才托举工程-中青年优秀科技人才培养计划项目（2023TJ-Z04）； 长沙市杰出创新青年培养计划项目（kq2406009）； 湖南省青年科技人才项目(2022RC1170)

Metabolic engineering for efficient squalene synthesis in Yarrowia lipolytica

PAN Yuqing1, ZHOU Han1, WANG Chong1, YANG Xiaona1, DUAN Xiyu1,HE Yuedong1, TIAN Yun1,2, LIU Huhu1   

  1. 1. College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China;
    2. Hunan Sweetmax Inc., Yongzhou 425900, China
  • Online:2026-02-18 Published:2026-02-27

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摘要： 为提升解脂耶氏酵母工程菌株YLM-1（Po1f、Δku70、ΔMHY1）生产角鲨烯的能力，首先通过敲除基因GUT2并过表达内源基因DGA1，成功构建脂滴形成增强的工程菌YLM-3，其合成角鲨烯的滴度达64.86 mg/L（8.43 mg/g）；其次运用IGG6序列构建多顺反子表达系统，并在其中过表达角鲨烯生物合成途径中相关关键基因ScHMG1、IDI、SQS，获得角鲨烯合成能力显著增强的工程菌YLM-4，其合成角鲨烯的滴度达491.28 mg/L（63.08 mg/g）；最后通过筛选发酵培养基发现，YLM-4菌株在YPD-70发酵培养基中发酵72 h合成角鲨烯的滴度高达1225.34 mg/L（62.96 mg/g）。研究实现了角鲨烯在解脂耶氏酵母中的高效合成，为后续合成角鲨烯下游衍生产品奠定坚实基础。

关键词: 解脂耶氏酵母, 角鲨烯, 代谢工程, 脂滴, 多顺反子表达系统

Abstract: To improve the level of squalene production by engineered strain YLM-1 (Po1f, Δku70, ΔMHY1) ofYarrowia lipolytica, theGUT2gene was first knocked out and the endogenousDGA1gene was overexpressed. This modification successfully yielded the engineered strain YLM-3. This strain exhibited enhanced lipid droplet formation and synthesized squalene at a titer of 64.86 mg/L (8.43 mg/g). Subsequently, a polycistronic expression system was constructed using theIGG6sequence to overexpress key genes of the squalene biosynthesis pathway (ScHMG1,IDI, andSQS). This strategy generated the engineered strain YLM-4, which demonstrated significantly enhanced squalene synthesis capacity, achieving a titer of 491.28 mg/L (63.08 mg/g). Finally, fermentation medium optimization revealed that strain YLM-4 could produce squalene at a titer of up to 1225.34 mg/L (62.96 mg/g) after 72 h of fermentation in YPD-70 fermentation medium. This study achieved efficient squalene synthesis inY. lipolytica, laying a solid foundation for the subsequent synthesis of downstream squalene derivatives.

Key words: Yarrowia lipolytica, squalene, metabolic engineering, lipid droplets, polycistronic expression system

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