{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:01:44Z","timestamp":1787313704253,"version":"build-2736575974"},"reference-count":112,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["113\u20102221\u2010E\u2010992\u2010006"],"award-info":[{"award-number":["113\u20102221\u2010E\u2010992\u2010006"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Squalene, a naturally occurring triterpene, has gained significant attention due to its critical role as an adjuvant in COVID\u201019 vaccines and its broad applications in pharmaceuticals, cosmetics, and nutraceuticals. This review explores the potential of squalene production, prompting a shift toward sustainable and innovative approaches. Key biosynthetic pathways across various organisms, including plants, fungi, and microalgae, are analyzed to identify efficient production systems as compared to fast\u2010growing heterotrophic thraustochytrids. Advanced strategies to enhance squalene yields are explored, including the use of chemical enhancers (methyl jasmonate), antioxidants (alpha\u2010tocopherol), cofactor recycling, and squalene epoxidase inhibitors (terbinafine). Additionally, the global market potential of squalene is assessed, highlighting its economic importance and growing demand in the healthcare and cosmetic industries. The challenges of large\u2010scale squalene production are addressed with a focus on sustainable alternatives to shark\u2010derived sources as a high ethical concern. By aligning with Sustainable Development Goals (SDG\u20103: Good Health and Well\u2010Being), squalene production supports advancements in vaccine development and biotechnological innovations. Future opportunities are highlighted, including novel applications in cancer therapy, functional foods, and anti\u2010aging products, offering pathways to harness its full potential while contributing to a sustainable bioeconomy.<\/jats:p>","DOI":"10.1002\/iub.70032","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T02:24:10Z","timestamp":1750904650000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Squalene: A High\u2010Value Compound for\n                    <scp>COVID<\/scp>\n                    \u201019 Vaccine Adjuvants and Beyond Pathways, Production Strategies, and Market Potential"],"prefix":"10.1002","volume":"77","author":[{"given":"Dileep","family":"Dasari","sequence":"first","affiliation":[{"name":"Institute of Aquatic Science and Technology, College of Hydrosphere, National Kaohsiung University of Science and Technology  Kaohsiung City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reeta Rani","family":"Singhania","sequence":"additional","affiliation":[{"name":"Institute of Aquatic Science and Technology, College of Hydrosphere, National Kaohsiung University of Science and Technology  Kaohsiung City Taiwan"},{"name":"Centre for Energy and Environmental Sustainability  Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashi Kant","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, College of Engineering Konkuk University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Di","family":"Dong","sequence":"additional","affiliation":[{"name":"Institute of Aquatic Science and Technology, College of Hydrosphere, National Kaohsiung University of Science and Technology  Kaohsiung City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7129-7548","authenticated-orcid":false,"given":"Anil Kumar","family":"Patel","sequence":"additional","affiliation":[{"name":"Institute of Aquatic Science and Technology, College of Hydrosphere, National Kaohsiung University of Science and Technology  Kaohsiung City Taiwan"},{"name":"Centre for Energy and Environmental Sustainability  Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-023-03689-y"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.01.011"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1519690113"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10030355"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tifs.2024.104392"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-54843-x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/elsc.202400003"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2022.03.008"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1829160"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13197-023-05740-0"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmars.2024.1371713"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.110430"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0958305X241272252"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2020.139691"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-019-1593-6"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/su16219142"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/md19100571"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10126-001-0016-3"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1227889"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.822254"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12020414"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201800136"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29215201"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2007.11.013"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.01.015"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.11.010"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0305-0491(00)00154-1"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/1567-1364.12107"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2021.107725"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.algal.2022.102946"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R700005200"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00050"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-016-2155-8"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2020.123991"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1992.tb00001.x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2019.101007"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2009.03.016"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbt.2010.04.005"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.15625\/0866-7160\/v39n3.8995"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2024.171734"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.4c09608"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/stresses4040041"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00299-019-02499-7"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.202400237"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00481-21"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/yea.3559"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2019.01.003"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.1212.12023"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1101\/2020.10.28.360032"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.1c00015"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21030716"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0270309"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-6915(99)00090-3"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-019-0043-x"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-016-7498-4"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.7b02945"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12051034"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.10.1145"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2001.01940.x"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-009-0301-2"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00988-06"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80213-5"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215593"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1213343109"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15143731"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.1c04978"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2020.124652"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2023.130233"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.900252"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-024-13051-3"},{"key":"e_1_2_11_72_1","first-page":"491","article-title":"Study of the Effect of Squalene Epoxidase Activity on Squalene Biosynthesis by Yeast Saccharomyces cerevisiae VGSh\u20102","volume":"2022","author":"Meshcheryakova O. L.","year":"2022","journal-title":"Knowledge E Life Sciences"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-018-2845-9"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-019-1415-x"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27082449"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10126-022-10139-7"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpy.12757"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.energy.2017.08.052"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090270"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2021.107897"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-021-01947-5"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(03)00454-0"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2015.1043501"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.04.048"},{"key":"e_1_2_11_85_1","first-page":"505","article-title":"Squalene, Biosynthesis and Its Role in Production of Bioactive Compounds, a Proper Scientific Challenge\u2014A Review","volume":"6","author":"Senbagalakshmi P.","year":"2019","journal-title":"Journal of Emerging Technologies and Innovative Research"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.5b01285"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcab.2020.101496"},{"key":"e_1_2_11_88_1","unstructured":"Fortune Business Insights \u201cSqualene Market Size Share & Industry Analysis by Source (Animal Plant and Biosynthetic) by End\u2010Use Industry (Cosmetics Food Pharmaceuticals and Others) and Regional Forecast 2025\u20132032 \u201dhttps:\/\/www.gii.tw\/report\/mama1355380\u2010squalene\u2010market\u2010by\u2010source\u2010biosynthetic\u2010end\u2010use.html."},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52687"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.589833"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.3390\/life11020103"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252313048"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2015.09.004"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2018.09.013"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2022.112779"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72704-1"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15030265"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.31989\/ffhd.v3i12.30"},{"issue":"1","key":"e_1_2_11_99_1","first-page":"29","article-title":"Squalene and Its Potential Clinical Uses","volume":"4","author":"Kelly G. S.","year":"1999","journal-title":"Alternative Medicine Review"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.29393"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2008.03133.x"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15010238"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-57308-3"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.2298\/VSP150116122F"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00157-17"},{"key":"e_1_2_11_106_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir641"},{"key":"e_1_2_11_107_1","doi-asserted-by":"publisher","DOI":"10.1002\/ski2.448"},{"key":"e_1_2_11_108_1","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2014.274"},{"key":"e_1_2_11_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiosc.2014.05.015"},{"key":"e_1_2_11_110_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adk7416"},{"key":"e_1_2_11_111_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2017.09.003"},{"key":"e_1_2_11_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiosc.2020.11.013"},{"key":"e_1_2_11_113_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.876649"}],"container-title":["IUBMB Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iub.70032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T09:43:36Z","timestamp":1754905416000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/iub.70032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":112,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/iub.70032"],"URL":"https:\/\/doi.org\/10.1002\/iub.70032","archive":["Portico"],"relation":{},"ISSN":["1521-6543","1521-6551"],"issn-type":[{"value":"1521-6543","type":"print"},{"value":"1521-6551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2025-02-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70032"}}