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High-level recombinant production of squalene using selected Saccharomyces cerevisiae strains

  • Metabolic Engineering and Synthetic Biology - Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

For recombinant production of squalene, which is a triterpenoid compound with increasing industrial applications, in microorganisms generally recognized as safe, we screened Saccharomyces cerevisiae strains to determine their suitability. A strong strain dependence was observed in squalene productivity among Saccharomyces cerevisiae strains upon overexpression of genes important for isoprenoid biosynthesis. In particular, a high level of squalene production (400 ± 45 mg/L) was obtained in shake flasks with the Y2805 strain overexpressing genes encoding a bacterial farnesyl diphosphate synthase (ispA) and a truncated form of hydroxyl-3-methylglutaryl-CoA reductase (tHMG1). Partial inhibition of squalene epoxidase by terbinafine further increased squalene production by up to 1.9-fold (756 ± 36 mg/L). Furthermore, squalene production of 2011 ± 75 or 1026 ± 37 mg/L was obtained from 5-L fed-batch fermentations in the presence or absence of terbinafine supplementation, respectively. These results suggest that the Y2805 strain has potential as a new alternative source of squalene production.

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Acknowledgements

This research was supported by a Grant from the KRIBB Research Initiative Program and by a National Research Foundation of Korea (NRF) Grant from the Korea government (MSIP) (Grant no. NRF-2016R1A2B4009432). This work was also supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries (IPET) through the Animal Disease Management Technology Development Program funded by the Ministry of Agriculture, Food, and Rural Affairs (MAFRA; 316043-3).

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Authors and Affiliations

  1. Biotechnology Process Engineering Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, 28116, Republic of Korea

    Jong Yun Han, Sung Hwa Seo, Jae Myeong Song, Hongweon Lee & Eui-Sung Choi

  2. Department of Bioprocess Engineering, KRIBB School of Biotechnology, Korea University of Science and Technology (UST), Daejeon, 34113, Republic of Korea

    Jong Yun Han, Jae Myeong Song, Hongweon Lee & Eui-Sung Choi

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  1. Jong Yun Han
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Correspondence to Eui-Sung Choi.

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Han, J.Y., Seo, S.H., Song, J.M. et al. High-level recombinant production of squalene using selected Saccharomyces cerevisiae strains. J Ind Microbiol Biotechnol 45, 239–251 (2018). https://doi.org/10.1007/s10295-018-2018-4

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  • DOI: https://doi.org/10.1007/s10295-018-2018-4

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