{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:42:27Z","timestamp":1788579747620,"version":"build-2803163510"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010037","name":"Chongqing Municipal Youth Science and Technology Talent Training Project","doi-asserted-by":"publisher","award":["cstc2021ycjh-bgzxm0201"],"award-info":[{"award-number":["cstc2021ycjh-bgzxm0201"]}],"id":[{"id":"10.13039\/501100010037","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Musk is a blackish-brown solid used in traditional Chinese medicine with a unique and intense scent. Limited evidence on its function and pathways is available from databases due to the complexity, variability, and derivativity of chemical composition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study, musk samples from three different stages during maturation: the end of June (group A), August (group B), and October (group C) were harvested from six male forest musk deer. A gas chromatography and mass spectrometry (GC-MS) approach was used to explore the chemical composition. Results indicated the presence of 66 known and 14 unknown chemicals, including 29 aromatic compounds. Lipids (51.52%), organic oxygen compounds (28.79%), and organoheterocyclic compounds (12.12%) were the most abundant substances. A total of 13 differential metabolites were found, including four macrocyclic ketones and six androgens and derivatives that increased as musk matured. Biosynthesis of unsaturated fatty acids was enriched in differential metabolites across stages. Tetracosanoic acid, methyl ester, and TES1 [EC: 3.1.2.2] participated in the biosynthesis of muscone. A total of nine chemicals and six steroidogenic enzymes participated in steroid hormone biosynthesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study annotates and defines metabolites in musk systematically, macrocyclic ketones (9.09%) and lipids (51.52%) were categorized unambiguously, suggesting that previous studies have underestimated the lipid content in musk, and critical role for lipid metabolism in musk gland development and odor profile formation. The high lipid content may reflect energy storage for glandular activity or serve as precursors for volatile compound synthesis, offering new mechanistic insights into musk maturation. Therefore, we preliminarily decipher the biosynthetic pathways of muscone and steroids through providing involved enzymes and metabolites. These results will deepen the understanding of the composition of natural musk and offer new theoretical insights to promote the comprehensive use of this resource.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1503138","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:13:07Z","timestamp":1745799187000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Elucidating metabolites and biosynthetic pathways during musk maturation: insights from forest musk deer"],"prefix":"10.3389","volume":"16","author":[{"given":"Hang","family":"Jie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helin","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guijun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejun","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/s11306-018-1367-3","article-title":"Guidelines and considerations for the use of system suitability and quality control samples in mass spectrometry assays applied in untargeted clinical metabolomic studies","volume":"14","author":"Broadhurst","year":"2018","journal-title":"Metabolomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1007\/s11626-018-0268-0","article-title":"Isolation, primary culture, and morphological characterization of gland epithelium from forest musk deer (Moschus berezovskii)","volume":"54","author":"Chen","year":"2018","journal-title":"Vitro Cell Dev. Biol. Anim."},{"key":"B3","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13020-022-00594-8","article-title":"From non-targeted to targeted GC-MS metabolomics strategy for identification of TCM preparations containing natural and artificial musk","volume":"17","author":"Ding","year":"2022","journal-title":"Chin. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1650031","DOI":"10.1142\/s0218213016500317","article-title":"A fuzzy graph framework for initializing k-means","volume":"25","author":"Drakopoulos","year":"2016","journal-title":"Int. J. Artif. Intell. Tools"},{"key":"B5","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1039\/d2np00067a","article-title":"The scent chemistry of butterflies","volume":"40","author":"Ehlers","year":"2023","journal-title":"Nat. Prod. Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1507\/endocrj.EJ18-0211","article-title":"Sex hormones play roles in determining musk composition during the early stages of musk secretion by musk deer (Moschus berezovskii)","volume":"65","author":"Fan","year":"2018","journal-title":"Endocr. J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1156138","DOI":"10.3389\/fcell.2023.1156138","article-title":"Integrated multi-omics analysis reveals insights into Chinese forest musk deer (Moschus berezovskii) genome evolution and musk synthesis","volume":"11","author":"Feng","year":"2023","journal-title":"Front. Cell Dev. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1271\/bbb.66.1389","article-title":"Synthesis of (R)- and (S)- muscone","volume":"66","author":"Fujimoto","year":"2002","journal-title":"Biochemistry"},{"key":"B9","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1017\/s0376892900000369","article-title":"Decline of musk deer in China and prospects for management","volume":"27","author":"Geng","year":"2000","journal-title":"Environ. Conserv."},{"key":"B10","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.ygcen.2017.09.015","article-title":"Seasonal expression of P450c17 and 5\u03b1-reductase-2 in the scented gland of male muskrats (Ondatra zibethicus)","volume":"254","author":"Han","year":"2017","journal-title":"Gen. Comp. Endocrinol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/166262a0","article-title":"Musk and the musk deer","volume":"166","author":"Hawkins","year":"","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/166262a0","article-title":"Musk and the musk deer","volume":"166","author":"Hawkins","year":"","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/hta16030","article-title":"A systematic review of prevention and intervention strategies for populations at high risk of engaging in violent behaviour: update 2002-8","volume":"16","author":"Hockenhull","year":"2012","journal-title":"Health Technol. Asses"},{"key":"B15","doi-asserted-by":"publisher","first-page":"106026","DOI":"10.1016\/j.jsbmb.2021.106026","article-title":"Androgen plays an important role in regulating the synthesis of pheromone in the scent gland of muskrat","volume":"217","author":"Jiang","year":"2022","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"4522","DOI":"10.4268\/cjcmm20142309","article-title":"Research progress on musk secretion mechanism of forest musk deer","volume":"39","author":"Jie","year":"2014","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"B18","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3969\/j.issn.1001-1528.2021.01.028","article-title":"Variation of chemical constituents in musk harvested at different maturity stages (in Chinese)","volume":"43","author":"Jie","year":"2021","journal-title":"Chin. Tradit. Pat. Medcine"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1002\/jssc.201200946","article-title":"Fast and direct quantification of underivatized muscone by ultra performance liquid chromatography coupled with evaporative light scattering detection","volume":"36","author":"Jin","year":"2013","journal-title":"J. Sep. Sci."},{"key":"B20","volume-title":"Aldehyde, ketone und chinone","author":"Latscha","year":"2016"},{"key":"B21","doi-asserted-by":"publisher","first-page":"18975","DOI":"10.1038\/srep18975","article-title":"The musk chemical composition and microbiota of Chinese forest musk deer males","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3048","DOI":"10.3389\/fmicb.2018.03048","article-title":"Microbiota changes in the musk gland of male forest musk deer during musk maturation","volume":"9","author":"Li","year":"2018","journal-title":"Front. Microbiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1126\/science.1174621","article-title":"Lipid rafts as a membrane-organizing principle","volume":"327","author":"Lingwood","year":"2010","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e22742","DOI":"10.1096\/fj.202201372R","article-title":"Single-nucleus RNA and ATAC sequencing uncovers the molecular and cellular characteristics in the musk gland of Chinese forest musk deer (Moschus berezovskii)","volume":"37","author":"Liu","year":"2023","journal-title":"FASEB J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13020-021-00457-8","article-title":"Zoology, chemical composition, pharmacology, quality control and future perspective of Musk (Moschus): a review","volume":"16","author":"Liu","year":"2021","journal-title":"Chin. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"105433","DOI":"10.1016\/j.jsbmb.2019.105433","article-title":"Seasonal expressions of androgen receptor, estrogen receptors, 5\u03b1-reductases and P450arom in the epididymis of the male muskrat (Ondatra zibethicus)","volume":"194","author":"Liu","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"114799","DOI":"10.1016\/j.jep.2021.114799","article-title":"Chemical compositions and pharmacological activities of natural musk (Moschus) and artificial musk","volume":"284","author":"Lv","year":"2022","journal-title":"A Rev."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1055\/s-0032-1316566","article-title":"Formation of five- and six-membered heterocyclic rings under radical cyclization conditions","volume":"44","author":"Majumdar","year":"2012","journal-title":"Synthesis Int. J. Methods Synthetic Org. Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1080\/19440049.2013.815807","article-title":"Are Chileans exposed to dietary furan?","volume":"30","author":"Mariotti","year":"2013","journal-title":"Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess."},{"key":"B30","doi-asserted-by":"publisher","first-page":"S142","DOI":"10.1016\/j.fct.2011.07.041","article-title":"Fragrance material review on cyclopentadecanone","volume":"49","author":"McGintyc","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1126\/science.335.6073.1168-a","article-title":"Asian medicine: exploitation of wildlife","volume":"335","author":"Meng","year":"2012","journal-title":"Science"},{"key":"B32","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nature10602","article-title":"Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia","volume":"481","author":"Metallo","year":"2011","journal-title":"Nature"},{"key":"B33","volume-title":"Commission CP: Pharmacopoeia of the People's Republic of China","year":"2020"},{"key":"B34","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1016\/j.theriogenology.2011.04.018","article-title":"The reproductive performance of female Forest musk deer (Moschus berezovskii) in captivity","volume":"76","author":"Qi","year":"2011","journal-title":"Theriogenology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1758-2946-6-13","article-title":"TCMSP: a database of systems pharmacology for drug discovery from herbal medicines","volume":"6","author":"Ru","year":"2014","journal-title":"J. Cheminform"},{"key":"B36","doi-asserted-by":"publisher","first-page":"241","DOI":"10.5487\/TR.2015.31.3.241","article-title":"Furan in thermally processed foods - a review","volume":"31","author":"Seok","year":"2015","journal-title":"Toxicol. Res."},{"key":"B37","volume-title":"The musk deer in China (in Chinese)","author":"Shen","year":"2007"},{"key":"B38","volume-title":"Dictionary of food compounds with CD-ROM: additives, flavors, and ingredients","author":"Shmuel","year":"2004"},{"key":"B39","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/35036052","article-title":"Lipid rafts and signal transduction","volume":"1","author":"Simons","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/BF01020352","article-title":"Musk deer (Moschus moschiferus): reinvestigation of main lipid components from preputial gland secretion","volume":"13","author":"Sokolov","year":"1987","journal-title":"J. Chem. Ecol."},{"key":"B41","first-page":"2472","article-title":"Quantitative analysis of musk components by gas chromatography\/mass spectrometry (in Chinese)","volume":"28","author":"Su","year":"2009","journal-title":"Sichuan J. Zoology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1037\/0033-2909.83.4.505","article-title":"Mammalian scent gland marking and social behavior","volume":"83","author":"Thiessen","year":"1976","journal-title":"Psychol. Bull."},{"key":"B43","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1021\/ac051441+","article-title":"Chemical speciation of iron in seawater by cathodic stripping voltammetry with dihydroxynaphthalene","volume":"78","author":"van den Berg","year":"2006","journal-title":"Anal. Chem."},{"key":"B44","doi-asserted-by":"publisher","first-page":"113120","DOI":"10.1016\/j.jep.2020.113120","article-title":"Pharmacological effects and mechanisms of muscone","volume":"262","author":"Wang","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"9913055","DOI":"10.1155\/2021\/9913055","article-title":"Binary eluent based vortex-assisted matrix solid-phase dispersion for the extraction and determination of multicomponent from musk by gas chromatography-mass spectrometry","volume":"2021","author":"Wang","year":"","journal-title":"J. Anal. methods Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"9913055","DOI":"10.1155\/2021\/9913055","article-title":"Binary eluent based vortex-assisted matrix solid-phase dispersion for the extraction and determination of multicomponent from musk by gas chromatography-mass spectrometry","volume":"2021","author":"Wang","year":"","journal-title":"J. Anal. Methods Chem."},{"key":"B62","doi-asserted-by":"publisher","first-page":"giaf006","DOI":"10.1093\/gigascience\/giaf006","article-title":"Multiomics analysis provides insights into musk secretion in muskrat and musk deer","volume":"14","author":"Wang","year":"2025","journal-title":"GigaScience"},{"key":"B47","doi-asserted-by":"publisher","first-page":"121893","DOI":"10.1016\/j.envpol.2023.121893","article-title":"Global distribution and ecological risk assessment of synthetic musks in the environment","volume":"331","author":"Wang","year":"2023","journal-title":"Environ. Pollut."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1111\/1751-7915.14002","article-title":"The essential differences in microbial and chemical components of musk of different qualities secreted by captive male forest musk deer (Moschus berezovskii)","volume":"15","author":"Wang","year":"2022","journal-title":"Microb. Biotechnol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/nrd.2016.32","article-title":"Emerging applications of metabolomics in drug discovery and precision medicine","volume":"15","author":"Wishart","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"B50","volume-title":"The musk deer of China (in Chinese)","author":"Wu","year":"2006"},{"key":"B51","doi-asserted-by":"publisher","first-page":"2228","DOI":"10.3390\/cells11142228","article-title":"Mass spectrometry imaging of lipids in the scent glands of muskrat (Ondatra zibethicus) in different reproductive statuses","volume":"11","author":"Xie","year":"2022","journal-title":"Cells"},{"key":"B52","doi-asserted-by":"publisher","first-page":"105766","DOI":"10.1016\/j.jsbmb.2020.105766","article-title":"Seasonal expressions of SF-1, StAR and P450scc in the scent glands of the muskrats (Ondatra zibethicus)","volume":"204","author":"Xie","year":"2020","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1322316","DOI":"10.3389\/fmicb.2024.1322316","article-title":"Chemical composition and microbiota changes across musk secretion stages of forest musk deer","volume":"15","author":"Xu","year":"2024","journal-title":"Front. Microbiol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/s0006-3207(02)00159-3","article-title":"Conservation status and causes of decline of musk deer (Moschus spp.) in China","volume":"109","author":"Yang","year":"2003","journal-title":"Biol. Conserv."},{"key":"B55","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/s0955-2863(00)00117-0","article-title":"Antioxidant and pro-oxidant effects of lycopene in comparison with beta-carotene on oxidant-induced damage in Hs68 cells","volume":"11","author":"Yeh","year":"2000","journal-title":"J. Nutr. Biochem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"3761","DOI":"10.1007\/s11756-021-00879-7","article-title":"Musk secretion of endangered Alpine musk deer (Moschus chrysogaster): muscone content and the relationships to age, health, mating history and enclosure condition","volume":"76","author":"Yuan","year":"2021","journal-title":"Biologia."},{"key":"B57","first-page":"1","article-title":"A method for synthesizing musketone from gene-edited yeast in vitro","author":"Zhang","year":"2022","journal-title":"China"},{"key":"B58","doi-asserted-by":"publisher","first-page":"e0245677","DOI":"10.1371\/journal.pone.0245677","article-title":"Study of compositions of musks in different types secreted by forest musk deer (Moschus berezovskii)","volume":"16","author":"Zhang","year":"2021","journal-title":"PLoS One"},{"key":"B61","doi-asserted-by":"publisher","first-page":"868","DOI":"10.3969\/j.issn.1001-1528.2002.11.017","article-title":"Quantitative analysis for multi-components of musk by gas chromatography\/mass spectrometry","volume":"24","author":"Zhang","year":"2002","journal-title":"Chinese Traditional Patent Medicine."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.13313\/j.issn.1673-4890.20191126001","article-title":"Determination and analysis of muscone content in musk produced by captive forest musk deer (in Chinese)","volume":"22","author":"Zheng","year":"2020","journal-title":"Mod. Chin. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1038\/s41396-021-00905-1","article-title":"Symbiotic bacteria mediate volatile chemical signal synthesis in a large solitary mammal species","volume":"15","author":"Zhou","year":"2021","journal-title":"ISME J."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1503138\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:13:11Z","timestamp":1745799191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1503138\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,28]]},"references-count":60,"alternative-id":["10.3389\/fphar.2025.1503138"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1503138","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,28]]},"article-number":"1503138"}}