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Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production

Author

Listed:
  • John Blazeck

    (The University of Texas at Austin)

  • Andrew Hill

    (The University of Texas at Austin)

  • Leqian Liu

    (The University of Texas at Austin)

  • Rebecca Knight

    (Section of Molecular, Cell and Developmental Biology, The University of Texas at Austin)

  • Jarrett Miller

    (The University of Texas at Austin)

  • Anny Pan

    (The University of Texas at Austin)

  • Peter Otoupal

    (The University of Texas at Austin)

  • Hal S. Alper

    (The University of Texas at Austin
    Institute for Cellular and Molecular Biology, The University of Texas at Austin)

Abstract

Economic feasibility of biosynthetic fuel and chemical production hinges upon harnessing metabolism to achieve high titre and yield. Here we report a thorough genotypic and phenotypic optimization of an oleaginous organism to create a strain with significant lipogenesis capability. Specifically, we rewire Yarrowia lipolytica’s native metabolism for superior de novo lipogenesis by coupling combinatorial multiplexing of lipogenesis targets with phenotypic induction. We further complete direct conversion of lipid content into biodiesel. Tri-level metabolic control results in saturated cells containing upwards of 90% lipid content and titres exceeding 25 g l−1 lipids, which represents a 60-fold improvement over parental strain and conditions. Through this rewiring effort, we advance fundamental understanding of lipogenesis, demonstrate non-canonical environmental and intracellular stimuli and uncouple lipogenesis from nitrogen starvation. The high titres and carbon-source independent nature of this lipogenesis in Y. lipolytica highlight the potential of this organism as a platform for efficient oleochemical production.

Suggested Citation

  • John Blazeck & Andrew Hill & Leqian Liu & Rebecca Knight & Jarrett Miller & Anny Pan & Peter Otoupal & Hal S. Alper, 2014. "Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4131
    DOI: 10.1038/ncomms4131
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    Cited by:

    1. Dipankar Baisya & Adithya Ramesh & Cory Schwartz & Stefano Lonardi & Ian Wheeldon, 2022. "Genome-wide functional screens enable the prediction of high activity CRISPR-Cas9 and -Cas12a guides in Yarrowia lipolytica," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Bao, Wenjun & Li, Zifu & Wang, Xuemei & Gao, Ruiling & Zhou, Xiaoqin & Cheng, Shikun & Men, Yu & Zheng, Lei, 2021. "Approaches to improve the lipid synthesis of oleaginous yeast Yarrowia lipolytica: A review," Renewable and Sustainable Energy Reviews, Elsevier, vol. 149(C).
    3. Robles-Iglesias, Raúl & Naveira-Pazos, Cecilia & Fernández-Blanco, Carla & Veiga, María C. & Kennes, Christian, 2023. "Factors affecting the optimisation and scale-up of lipid accumulation in oleaginous yeasts for sustainable biofuels production," Renewable and Sustainable Energy Reviews, Elsevier, vol. 171(C).
    4. Shihui Yang & Wei Wang & Hui Wei & Stefanie Van Wychen & Philip T. Pienkos & Min Zhang & Michael E. Himmel, 2016. "Comparison of Nitrogen Depletion and Repletion on Lipid Production in Yeast and Fungal Species," Energies, MDPI, vol. 9(9), pages 1-12, August.
    5. Ko, Ja Kyong & Lee, Jae Hoon & Jung, Je Hyeong & Lee, Sun-Mi, 2020. "Recent advances and future directions in plant and yeast engineering to improve lignocellulosic biofuel production," Renewable and Sustainable Energy Reviews, Elsevier, vol. 134(C).
    6. Svetlana V. Kamzolova & Igor G. Morgunov, 2021. "Physiological, Biochemical and Energetic Characteristics of Torulaspora globosa , a Potential Producer of Biofuel," Energies, MDPI, vol. 14(11), pages 1-9, May.
    7. Yook, Sang Do & Kim, Jiwon & Woo, Han Min & Um, Youngsoon & Lee, Sun-Mi, 2019. "Efficient lipid extraction from the oleaginous yeast Yarrowia lipolytica using switchable solvents," Renewable Energy, Elsevier, vol. 132(C), pages 61-67.
    8. Das, Manali & Patra, Pradipta & Ghosh, Amit, 2020. "Metabolic engineering for enhancing microbial biosynthesis of advanced biofuels," Renewable and Sustainable Energy Reviews, Elsevier, vol. 119(C).

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