Cardiovascular disease (CVD) is one of the most severe diseases that took away millions of lives.
In 2019, an estimated 17.9 million people died from CVD, representing 32% of all global deaths. (WHO official website).
The living habits nowadays cause the excess intake of cholesterol from the modern diet, inducing the accumulation of oxidized low-density lipoproteins ( LDL ) in arteries.
The oxidized LDL accumulation impedes blood flow and damages the arteries, which leads to atherosclerosis, the severe CVD (Berger and Naseem 2022).
Recently, the daily intake of eicosapentaenoic acid (EPA) has been proven to reduce CVD efficiently and severe CVD causes death (Peter, Joho et al. 2022).
EPA reduces CVDs in two aspects. In arteries, EPA can split heme into biliverdin, free iron, and carbon monoxide to clean the free radicals and reduce oxidative LDL accumulation. EPA can also relax the surrounding smooth muscle to avoid severe CVDs by enhancing nitric oxide production (Sherratt, Libby et al. 2022).
However, the major source of EPA, marine fishes, is the end consumer in the food chain, and the accumulation of heavy metals and microplastics is not rare in marine fishes.
Therefore, the development of a new EPA source is necessary to cover future consumption and avoid potential contamination (Hong, Lumibao et al. 2015, Abbasi, Soltani et al. 2018, Benvenga, Fama et al. 2022).
To generate an EPA supplement without potential contaminants, our team applied synthetic biology to produce pure EPA.
  • EPA producing gene
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    Previous research has shown that a combination of the pfa genes of deep-sea bacteria Moritella marina MP-1 and Shewanella pneumatophori SCRC-2738 can produce EPA in E. coli.
  • Gene engineering
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    We cloned the pfa A, pfa C, pfa D, and pfa E genes from MP-1, and pfa B gene from SCRC-2738. All these five pfa genes are expressed in E. coli to produce EPA (Orikasa, Tanaka et al. 2009).
    Cost is a core point for running a business. To reduce the cost, we increase the raw material of EPA in E. coli by expressing ACC complex, and add the chemical cerulenin to inhibit the competing fatty acid synthesis pathway.
  • Acc complex
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    The ACC complex can increase malonyl-CoA, the raw material of EPA. The ACC genes (AccBC, AccD1, and AccE) were therefore cloned into the target plasmid and expressed in E. coli (Giner-Robles, Lazaro et al. 2018).
  • Chemical cerulenin
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    Cerulenin inhibits the fatty acid synthesis pathway that competes with pfa genes in E. coli, thus increasing the efficiency of EPA production (Satoh, Ozaki et al. 2020).
    Integrated to the society
    To integrate our project into society, we share CVD knowledge with the elderly through campus walking activity and synthetic biology with teenagers through open lab activity.
    We also launched a web game for all ages, which overcomes the urban-rural gap to introduce knowledge about synthetic biology.
    To polish our project, we first discussed with other iGEM teams and gathered feedback from experts and potential EPA users. To start a business in the future, we held an innovation & entrepreneurship competition to bridge Taiwan iGEM teams with biotech entrepreneurs and synthetic biologists.
    Together, PACOmega is an inclusive project dedicated to raising public awareness of CVD and eliminating the distance between synthetic biology and the public. In addition, we keep searching for opportunities and preparing for future entrepreneurship to produce EPA supplements - The Pure Artery Omega, PACOmega.
  • Abbasi, S., N. Soltani, B. Keshavarzi, F. Moore, A. Turner and M. Hassanaghaei (2018). "Microplastics in different tissues of fish and prawn from the Musa Estuary, Persian Gulf." Chemosphere 205: 80-87.
  • Benvenga, S., F. Fama, L. G. Perdichizzi, A. Antonelli, G. Brenta, F. Vermiglio and M. Moleti (2022). "Fish and the Thyroid: A Janus Bifrons Relationship Caused by Pollutants and the Omega-3 Polyunsaturated Fatty Acids." Front Endocrinol (Lausanne) 13: 891233.
  • Berger, M. and K. M. Naseem (2022). "Oxidised Low-Density Lipoprotein-Induced Platelet Hyperactivity-Receptors and Signalling Mechanisms." Int J Mol Sci 23(16).
  • Giner-Robles, L., B. Lazaro, F. de la Cruz and G. Moncalian (2018). "fabH deletion increases DHA production in Escherichia coli expressing Pfa genes." Microb Cell Fact 17(1): 88.
  • Hong, M. Y., J. Lumibao, P. Mistry, R. Saleh and E. Hoh (2015). "Fish Oil Contaminated with Persistent Organic Pollutants Reduces Antioxidant Capacity and Induces Oxidative Stress without Affecting Its Capacity to Lower Lipid Concentrations and Systemic Inflammation in Rats." J Nutr 145(5): 939-944.
  • Orikasa, Y., M. Tanaka, S. Sugihara, R. Hori, T. Nishida, A. Ueno, N. Morita, Y. Yano, K. Yamamoto, A. Shibahara, H. Hayashi, Y. Yamada, A. Yamada, R. Yu, K. Watanabe and H. Okuyama (2009). "pfaB products determine the molecular species produced in bacterial polyunsaturated fatty acid biosynthesis." FEMS Microbiol Lett 295(2): 170-176.
  • Peter P. Toth, M. John Chapman, Klaus G. Parhofer, John R. Nelson (2022). "Differentiating EPA from EPA/DHA in cardiovascular risk reduction "American Heart Journal Plus: Cardiology Research and Practice 17
  • Satoh, S., M. Ozaki, S. Matsumoto, T. Nabatame, M. Kaku, T. Shudo, M. Asayama and S. Chohnan (2020). "Enhancement of fatty acid biosynthesis by exogenous acetyl-CoA carboxylase and pantothenate kinase in Escherichia coli." Biotechnol Lett 42(12): 2595-2605.
  • Sherratt, S. C. R., P. Libby, D. L. Bhatt and R. P. Mason (2022). "A biological rationale for the disparate effects of omega-3 fatty acids on cardiovascular disease outcomes." Prostaglandins Leukot Essent Fatty Acids 182: 102450.
  • WHO official website: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)