Revealing the biosynthetic pathways of omega-3 fatty acids in marine microorganisms


Nippon Suisan Kaisha, Ltd. (President and CEO Shingo Hamada, Minato-ku, Tokyo, hereafter "Nissui") collaborated with Kyushu University, Miyazaki University, and Konan University*1 to investigate the biosynthetic pathways of omega-3 fatty acids*2 in marine microorganisms, such as those in the marine protists, Labyrinthulomycetes *3. Our study revealed that some species produce docosahexaenoic acid (DHA) through a pathway, which had not been previously identified. Furthermore, we showed that by disrupting the expression of certain genes, omega-3 fatty acids such as eicosapentaenoic acid (EPA) and n-3 DPA*4 can be produced by some Labyrinthulomycetes. This could be used to develop a method for sustainable production of omega-3 fatty acids using marine microorganisms at an industrial level. This study was published in Communications Biology (Springer-Nature) on 9th December 2021.
The demand for omega-3 fatty acids, such as EPA and DHA, which are known for their nutritional and medical benefits, is increasing worldwide. Nissui sells EPA, which is collected and refined as a functional raw material and sustainably sourced from a Peruvian anchovy species. To prepare for heightened demand, Nissui began to develop sustainable production method of EPA and DHA that does not rely solely on natural resources in 2006.
We closely investigated the DHA biosynthetic pathway in several species of Labyrinthulomycetes, a class of marine microorganisms known to produce omega-3 fatty acids. We found that members of the genus Parietichytrium sarkarianum*5 and Parietichytrium sp. could synthesize omega-3 fatty acids without "PolyKetide Synthase-like PUFA synthase enzyme complex*6" (Fig. A Type III), unlike previously known biosynthetic pathways in Labyrinthulomycetes (Fig. Type I and Type II). In this Type III pathway, three elongases and six desaturases converted palmitic acid to DHA via EPA and n-3 DPA (Fig. B). In addition, we found that by disrupting expression of certain genes, we can produce microbial oils containing omega-3 fatty acids aside from DHA, including EPA and n-3 DPA (Fig. B).

Microbial production of functional lipids is an industrialized process. Nissui aims to obtain a sustainable source of omega-3 fatty acids without genetic modification technology through further research on the new biosynthetic pathway revealed in this study.
This work was supported by the Science and Technology Research Promotion Program for Agriculture, Fisheries and Food Industry, Japan (26050A).

* 1 Makoto ITO and Yohei ISHIBASHI (Kyushu Univ.), Masahiro HAYASHI (Miyazaki Univ.), Daisuke HONDA (Konan Univ.) and others.

* 2 omega-3 fatty acids" are a type of polyunsaturated fatty acid, characterized by the presence of a double bond located three atoms away from the terminal methyl group in their chemical structure. EPA and DHA are common omega-3 fatty acids that are known to reduce the risk of heart disease, lower blood triglycerides, and alleviate rheumatoid arthritis symptoms.

*3 "Labyrinthulomycetes" is a unicellular eukaryote with a diameter of approximately 10 µm found in all marine environments, from coastal to open ocean, tropical to polar latitudes, and ocean surface to deep sea. Labyrinthulomycetes accumulates microbial oils containing high concentrations DHA into its cells; thus, it is considered as a potential candidate for sustainable omega-3 fatty acid source in marine ecosystems.

*4 "n-3 DPA" means omega-3 docosapentaenoic acid. It is an omega-3 fatty acid containing 22 carbons and 5 double bounds. It is also expected to be a new type of functional lipid.

*5 "Parietichytrium sarkarianum" is a species of Labyrinthulomycetes classified in the genus Parietichytrium.

*6 "PolyKetide Synthase-like PUFA synthase" is an enzyme complex comprising three to five subunits that catalyzes elongation and desaturation of fatty acids. This enzyme complex directly synthesizes PUFAs from acetyl-CoA and malonyl-CoA substrates with a few intermediates.

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