Applied Microbiology and Biotechnology

, Volume 103, Issue 5, pp 2181–2192 | Cite as

Enhanced itaconic acid production in Yarrowia lipolytica via heterologous expression of a mitochondrial transporter MTT

  • Chen Zhao
  • Zhiyong Cui
  • Xiangying Zhao
  • Jiaxiang Zhang
  • Lihe Zhang
  • Yanjun Tian
  • Qingsheng Qi
  • Jianjun LiuEmail author
Biotechnological products and process engineering


Itaconic acid, a promising platform chemical, has been applied in many fields of industrial production. As a potential candidate for itaconic acid production, Yarrowia lipolytica possesses several innate abilities such as the tolerance of low-pH and high-shear stress, fast growth rate, cultivation flexibility, and easy for genetic manipulation. Here, Y. lipolytica Po1f which was tested to show high tolerance to itaconic acid could accumulate itaconic acid (0.363 g/L) by expressing the Aspergillus terreus cis-aconitic acid decarboxylase (CAD). Then, we tried to improve the supply and transport of the immediate precursor cis-aconitic acid by overexpressing a series of genes; these results indicate that overexpression of mitochondrial cis-aconitate transporter MTT is beneficial to the itaconic acid biosynthesis in Y. lipolytica. Further culture optimization enabled 22.03 g/L of itaconic acid to be produced in bioreactors, about 60-fold improvement over the initial titer, which is the highest itaconic acid production achieved at low pH by yeast reported worldwide, to data. This study demonstrates the great potential of Y. lipolytica as an industrial platform for itaconic acid production.


Itaconic acid Yarrowia lipolytica Cis-aconitate decarboxylase Mitochondrial transporter 


Funding information

This study was funded by the key research and development plan of Shandong Province (2016ZDJS07A19) and the National High-tech R&D Program of China (863 Program) (2015AA021003).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2019_9627_MOESM1_ESM.pdf (173 kb)
ESM 1 (PDF 173 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Chen Zhao
    • 1
  • Zhiyong Cui
    • 2
  • Xiangying Zhao
    • 1
  • Jiaxiang Zhang
    • 1
  • Lihe Zhang
    • 1
  • Yanjun Tian
    • 1
  • Qingsheng Qi
    • 2
  • Jianjun Liu
    • 1
    Email author
  1. 1.Shandong Provincial Key Laboratory of Food and Fermentation Engineering, Shandong Food Ferment Industry Research & Design InstituteQilu University of Technology (Shandong Academy of Sciences)JinanPeople’s Republic of China
  2. 2.State Key Laboratory of Microbial TechnologyShandong UniversityQingdaoPeople’s Republic of China

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