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Jellyfish, which are ancient marine invertebrates with hundreds of millions of years of evolutionary history, have been in continuous contact with a diverse array of pathogenic microorganisms from seawater, which may give rise to a distinctive innate immune system and related defensive molecules. However, it is difficult and inefficient to isolate active ingredients directly from jellyfish for enrichment, though few jellyfish\u2010sourced antimicrobial peptides (AMPs) have been reported. In this study, we utilized transcriptomic big data with bioinformatic tools to dig deeper into potential antimicrobial components in jellyfish, and identified a new AMP JFP\u20102826 from <jats:styled-content style=\"fixed-case\"><jats:italic>Rhopilema esculentum<\/jats:italic><\/jats:styled-content>. The 20\u2010mer peptide exhibited an alpha\u2010helix structure and showed antimicrobial activity against selected bacterial strains; more importantly, JFP\u20102826 demonstrated good selectivity for marine\u2010specific <jats:italic>Vibrio<\/jats:italic> including <jats:styled-content style=\"fixed-case\"><jats:italic>Vibrio vulnificus<\/jats:italic><\/jats:styled-content>. Sequence analysis of the full\u2010length protein of JFP\u20102826 revealed that it is derived from the housekeeping gene glyceraldehyde\u20103\u2010phosphate dehydrogenase (GAPDH), which is probably produced through enzymatic cleavage of the N\u2010terminal fragment. This suggests that GAPDH of jellyfish might have a newly discovered antimicrobial\u2010related function that is conducted by releasing JFP\u20102826\u2010like cryptic peptides. JFP\u20102826 can be subjected to further structural modifications and optimizations to potentially become a potent lead peptide for the development of novel antimicrobial drugs treating infections of marine pathogens.<\/jats:p>","DOI":"10.1002\/psc.70011","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T09:37:43Z","timestamp":1741772263000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification and Characterization of a Novel GAPDH\u2010Derived Antimicrobial Peptide From Jellyfish"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2723-620X","authenticated-orcid":false,"given":"Jingwen","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmacy Bengbu Medical University  Bengbu China"},{"name":"Naval Medical Center Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Wound Infection and Drug, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical Center (Daping Hospital) Army Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueyue","family":"Li","sequence":"additional","affiliation":[{"name":"Naval Medical Center Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"The Third Department of Convalescence of Beidaihe Rehabilitation and Convalescence Center of PLA  Qinhuangdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Geng","sequence":"additional","affiliation":[{"name":"Naval Medical Center Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyi","family":"Wan","sequence":"additional","affiliation":[{"name":"Naval Medical Center Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Lu","sequence":"additional","affiliation":[{"name":"Naval Medical Center Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqing","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Bengbu Medical University  Bengbu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingke","family":"Wang","sequence":"additional","affiliation":[{"name":"Naval Medical Center Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jishun","family":"Yang","sequence":"additional","affiliation":[{"name":"Naval Medical Center Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2018.04.110"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3NP00031A"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00459"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmars.2022.1112595"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2024.12.002"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/md22050201"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsi.2019.09.028"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10010133"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.07.078"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac933"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.angen.2022.200137"},{"key":"e_1_2_12_13_1","first-page":"76","article-title":"In Vitro and in Vivo Antibacterial Activity of Tigecycline Against Vibrio Vulnificus","volume":"51","author":"Tang H. 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