PUFA synthase-independent DHA synthesis pathway in Parietichytrium sp. and its modification to produce EPA and n-3DPA

Yohei Ishibashi, Hatsumi Goda, Rie Hamaguchi, Keishi Sakaguchi, Takayoshi Sekiguchi, Yuko Ishiwata, Yuji Okita, Seiya Mochinaga, Shingo Ikeuchi, Takahiro Mizobuchi, Yoshitake Takao, Kazuki Mori, Kosuke Tashiro, Nozomu Okino, Daiske Honda, Masahiro Hayashi, Makoto Ito

Research output: Contribution to journalArticlepeer-review

Abstract

The demand for n-3 long-chain polyunsaturated fatty acids (n-3LC-PUFAs), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), will exceed their supply in the near future, and a sustainable source of n-3LC-PUFAs is needed. Thraustochytrids are marine protists characterized by anaerobic biosynthesis of DHA via polyunsaturated fatty acid synthase (PUFA-S). Analysis of a homemade draft genome database suggested that Parietichytrium sp. lacks PUFA-S but possesses all fatty acid elongase (ELO) and desaturase (DES) genes required for DHA synthesis. The reverse genetic approach and a tracing experiment using stable isotope-labeled fatty acids revealed that the ELO/DES pathway is the only DHA synthesis pathway in Parietichytrium sp. Disruption of the C20 fatty acid ELO (C20ELO) and ∆4 fatty acid DES (∆4DES) genes with expression of ω3 fatty acid DES in this thraustochytrid allowed the production of EPA and n-3docosapentaenoic acid (n-3DPA), respectively, at the highest level among known microbial sources using fed-batch culture.

Original languageEnglish
Article number1378
JournalCommunications Biology
Volume4
Issue number1
DOIs
Publication statusPublished - Dec 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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