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Enhancement of Squalene Production by Constitutive Expression of the 3-Hydroxy-3-Methylglutaryl-CoA Reductase in Aurantiochytrium sp. 18W-13a

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Abstract

Squalene has a wide range of applications in the industry sectors of dietary supplements, cosmetics, immunization, and pharmaceuticals. Yet, suitable organisms as the source of squalene are limited. It is reported that the thraustochytrid Aurantiochytrium sp. strain 18W-13a can accumulate high content of squalene. However, squalene production in this organism is fluctuated under various conditions and is not yet optimized for commercialization. In this organism, the mevalonate pathway supplies isopentenyl pyrophosphate, the initial substrate for squalene production. In this pathway, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) is the rate-limiting enzyme. We found that the HMGR activity had a strong positive correlation with the squalene contents in the strain. We constitutively expressed the HMGR in this organism and found that the transformant showed increased and stable production of squalene as well as carotenoids and biomass. These results clearly indicated that the HMGR expression is the bottleneck of squalene synthesis in Aurantiochytrium sp.

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Acknowledgements

The authors wish to thank Prof. Makoto M. Watanabe and Dr. Masaki Yoshida, who belonged to the Algal Biomass and Energy System Research and Development Center, the University of Tsukuba, for providing the Aurantiochytrium sp. 18W-13a. Furthermore, we acknowledge Prof. Ken-Ichiro Ishida of the University of Tsukuba for providing valuable suggestions, and, finally, emeritus Prof. Makoto Ito of the Kyushu University for providing the vectors for transformation.

Funding

This work was supported by the JSPS KAKENHI [grant numbers JP17H00800] and the JST OPERA [grant number JPMJOP1832].

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Authors and Affiliations

  1. Graduate School of Science and Technology, University of Tsukuba, Ibaraki, 305-8572, Japan

    Tianjing Yang

  2. Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan

    Darryl Joy Juntila, Naomichi Fujihara & Takashi Inada

  3. Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan

    Kohei Yoneda & Iwane Suzuki

  4. Algal Bio Co. Ltd, Kashiwa, Chiba, 277-0882, Japan

    Darryl Joy Juntila

  5. Chitose Laboratory Corporation, Kawasaki, Kanagawa, 216-0041, Japan

    Takashi Inada

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  1. Tianjing Yang
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Contributions

Tianjing Yang: methodology, investigation, validation, writing — original draft preparation, and writing — review and editing; Darryl Joy Juntila: methodology, investigation, and writing — review and editing; Naomichi Fujihara: methodology and investigation; Takashi Inada: methodology and data curation; Kohei Yoneda: methodology, data curation; Iwane Suzuki: conceptualization, methodology, writing — review and editing, supervision, project administration, and funding acquisition.

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Correspondence to Iwane Suzuki.

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Yang, T., Juntila, D.J., Fujihara, N. et al. Enhancement of Squalene Production by Constitutive Expression of the 3-Hydroxy-3-Methylglutaryl-CoA Reductase in Aurantiochytrium sp. 18W-13a. Mar Biotechnol 24, 733–743 (2022). https://doi.org/10.1007/s10126-022-10139-7

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