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Engineering fungal de novo fatty acid synthesis for short chain fatty acid production

Author

Listed:
  • Jan Gajewski

    (Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence ‘Macromolecular Complexes’, Goethe University Frankfurt)

  • Renata Pavlovic

    (Institute of Molecular Biosciences, Goethe University Frankfurt)

  • Manuel Fischer

    (Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence ‘Macromolecular Complexes’, Goethe University Frankfurt)

  • Eckhard Boles

    (Institute of Molecular Biosciences, Goethe University Frankfurt)

  • Martin Grininger

    (Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence ‘Macromolecular Complexes’, Goethe University Frankfurt)

Abstract

Fatty acids (FAs) are considered strategically important platform compounds that can be accessed by sustainable microbial approaches. Here we report the reprogramming of chain-length control of Saccharomyces cerevisiae fatty acid synthase (FAS). Aiming for short-chain FAs (SCFAs) producing baker’s yeast, we perform a highly rational and minimally invasive protein engineering approach that leaves the molecular mechanisms of FASs unchanged. Finally, we identify five mutations that can turn baker’s yeast into a SCFA producing system. Without any further pathway engineering, we achieve yields in extracellular concentrations of SCFAs, mainly hexanoic acid (C6-FA) and octanoic acid (C8-FA), of 464 mg l−1 in total. Furthermore, we succeed in the specific production of C6- or C8-FA in extracellular concentrations of 72 and 245 mg l−1, respectively. The presented technology is applicable far beyond baker’s yeast, and can be plugged into essentially all currently available FA overproducing microorganisms.

Suggested Citation

  • Jan Gajewski & Renata Pavlovic & Manuel Fischer & Eckhard Boles & Martin Grininger, 2017. "Engineering fungal de novo fatty acid synthesis for short chain fatty acid production," Nature Communications, Nature, vol. 8(1), pages 1-8, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14650
    DOI: 10.1038/ncomms14650
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    Cited by:

    1. M. Tanvir Rahman & M. Kristian Koski & Joanna Panecka-Hofman & Werner Schmitz & Alexander J. Kastaniotis & Rebecca C. Wade & Rik K. Wierenga & J. Kalervo Hiltunen & Kaija J. Autio, 2023. "An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. 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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