Polyunsaturated fatty acid production by Yarrowia lipolytica employing designed myxobacterial PUFA synthases

Katja Gemperlein, Demian Dietrich, Michael Kohlstedt, Gregor Zipf, Hubert S. Bernauer, Christoph Wittmann, Silke C. Wenzel and Rolf Müller ()
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Katja Gemperlein: Helmholtz Institute for Pharmaceutical Research Saarland and Helmholtz Centre for Infection Research
Demian Dietrich: Saarland University
Michael Kohlstedt: Saarland University
Gregor Zipf: ATG:biosynthetics GmbH
Hubert S. Bernauer: ATG:biosynthetics GmbH
Christoph Wittmann: Saarland University
Silke C. Wenzel: Saarland University
Rolf Müller: Helmholtz Institute for Pharmaceutical Research Saarland and Helmholtz Centre for Infection Research

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract Long-chain polyunsaturated fatty acids (LC-PUFAs), particularly the omega-3 LC-PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), have been associated with beneficial health effects. Consequently, sustainable sources have to be developed to meet the increasing demand for these PUFAs. Here, we demonstrate the design and construction of artificial PUFA biosynthetic gene clusters (BGCs) encoding polyketide synthase-like PUFA synthases from myxobacteria adapted for the oleaginous yeast Yarrowia lipolytica. Genomic integration and heterologous expression of unmodified or hybrid PUFA BGCs yielded different yeast strains with specific LC-PUFA production profiles at promising yield and thus valuable for the biotechnological production of distinct PUFAs. Nutrient screening revealed a strong enhancement of PUFA production, when cells were phosphate limited. This represents, to the best of our knowledge, highest concentration of DHA (16.8 %) in total fatty acids among all published PUFA-producing Y. lipolytica strains.

Date: 2019
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DOI: 10.1038/s41467-019-12025-8

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