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Expanding the product portfolio of fungal type I fatty acid synthases

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Abstract

Fungal type I fatty acid synthases (FASs) are mega-enzymes with two separated, identical compartments, in which the acyl carrier protein (ACP) domains shuttle substrates to catalytically active sites embedded in the chamber wall. We devised synthetic FASs by integrating heterologous enzymes into the reaction chambers and demonstrated their capability to convert acyl-ACP or acyl-CoA from canonical fatty acid biosynthesis to short/medium-chain fatty acids and methyl ketones.

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Figure 1: Design and strategy for engineering fungal fatty acid synthases (FASs) to synthesize tailored oleochemicals.
Figure 2: Synthesis of oleochemicals by engineered fungal FASs.

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Acknowledgements

This work was funded by grants from Total New Energies, the Novo Nordisk Foundation, and the Knut and Alice Wallenberg Foundation to J.N. and from the National Natural Science Foundation of China to Z.K.Z. (No. 21325627). We thank H.-J. Schüller (Ernst-Moritz-Arndt-Universität Greifswald, Germany) for sharing the PWY12 strain; J.L. Collier (Stony Brook University, USA) for providing genomic DNA of A. kerguelense; C. Song and J. Li (Dalian Institute of Chemical Physics), respectively, for the MALDI–TOF Mass Spectrometry analysis and ultracentrifugation; and S. Khoomrung and the Chalmers Mass Spectrometry Infrastructure (J. Karlsson and J. Kindbom) for assistance with GC–MS analysis. We also appreciate the help from and/or discussion with S. Zhang, W. Liu, X. Lin, V. Siewers, Y. Chen, M. Fischer, Z. Dai, N.A. Buijs, P. Teixeira and O. Vidalin.

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Authors and Affiliations

  1. Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden

    Zhiwei Zhu, Yongjin J Zhou, Anastasia Krivoruchko & Jens Nielsen

  2. Division of Biotechnology, Dalian Institute of Chemical Physics, CAS, Dalian, China

    Zhiwei Zhu & Zongbao K Zhao

  3. Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, Gothenburg, Sweden

    Zhiwei Zhu, Yongjin J Zhou, Anastasia Krivoruchko & Jens Nielsen

  4. Biopetrolia AB, Systems and Synthetic Biology, Chalmers University of Technology, Gothenburg, Sweden

    Anastasia Krivoruchko & Jens Nielsen

  5. Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence for Macromolecular Complexes, Goethe University Frankfurt, Frankfurt am Main, Germany

    Martin Grininger

  6. Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, CAS, Dalian, China

    Zongbao K Zhao

  7. Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark

    Jens Nielsen

  8. Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden

    Jens Nielsen

Authors
  1. Zhiwei Zhu
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  2. Yongjin J Zhou
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  3. Anastasia Krivoruchko
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  4. Martin Grininger
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  5. Zongbao K Zhao
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  6. Jens Nielsen
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Contributions

Z.Z., Z.K.Z. and J.N. conceived this study. Z.Z. designed and performed most of the experiments and analyzed the data. Z.Z. and Z.K.Z. performed biochemical study of Rhodosporidium fatty acid synthase (FAS) at Dalian Institute of Chemical Physics. Y.J.Z. participated in the plasmid construction and product quantification. A.K. assisted with data analysis and interpretation. M.G. developed the ketoacyl synthase (KS) mutation. Z.Z. and J.N. wrote the manuscript. All authors revised and approved the manuscript.

Corresponding authors

Correspondence to Zongbao K Zhao or Jens Nielsen.

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Competing interests

Z.Z., A.K. and J.N. are listed as co-inventors on a patent application related to fatty acid production. J.N. and A.K. are shareholders in Biopetrolia AB.

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Supplementary Text and Figures

Supplementary Results, Supplementary Tables 1–7 and Supplementary Figures 1–9. (PDF 7299 kb)

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Zhu, Z., Zhou, Y., Krivoruchko, A. et al. Expanding the product portfolio of fungal type I fatty acid synthases. Nat Chem Biol 13, 360–362 (2017). https://doi.org/10.1038/nchembio.2301

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