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Here, we produced recombinant BaMtx (rBaMtx), a Lys49-PLA2 homologue from Bothrops atrox, in the Pichia pastoris KM71 expression system and evaluated whether its biochemical and biological properties were preserved. rBaMtx was secreted into the culture medium, purified by cation-exchange chromatography, and characterized by SDS-PAGE, Western blotting, RP-HPLC (85.9% purity), and MALDI-TOF mass spectrometry, confirming a molecular mass of 13,821 Da. Despite lacking PLA2 activity, rBaMtx retained pronounced myotoxicity in vivo, inducing dose-dependent plasma creatine kinase release and skeletal muscle damage comparable to or greater than native BaMtx. In vitro, rBaMtx reduced viability of murine 4T1 breast carcinoma cells (IC50 = 60.94 \u00b5g\/mL), altered cell morphology, modestly increased IL-1\u03b2 release, and produced context-dependent effects in paired human tumor and non-tumor cell models, differing from native BaMtx and crude venom. These findings establish rBaMtx as a reproducible model for investigating the mechanisms and biomedical potential of catalytically inactive Lys49-PLA2 homologues.<\/jats:p>","DOI":"10.3390\/toxins18080338","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T08:04:59Z","timestamp":1785744299000},"page":"338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recombinant BaMtx Preserves the Biological Properties of a Lys49 Phospholipase A2 from Bothrops atrox and Reveals Differential Responses in Tumor and Non-Tumor Cell Models"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9385-6921","authenticated-orcid":false,"given":"Daniel","family":"Torrej\u00f3n","sequence":"first","affiliation":[{"name":"Grupo de Investigaci\u00f3n Toxinas de Origen Animal y sus Antivenenos (TOXIVEN), Laboratorio de Biolog\u00eda Molecular, Facultad de Ciencias Biol\u00f3gicas, Universidad Nacional Mayor de San Marcos, Av. Venezuela Cdra. 34 S\/N, Ciudad Universitaria, Lima 15081, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9726-6686","authenticated-orcid":false,"given":"Angie","family":"Regalado","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n Toxinas de Origen Animal y sus Antivenenos (TOXIVEN), Laboratorio de Biolog\u00eda Molecular, Facultad de Ciencias Biol\u00f3gicas, Universidad Nacional Mayor de San Marcos, Av. Venezuela Cdra. 34 S\/N, Ciudad Universitaria, Lima 15081, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7883-3916","authenticated-orcid":false,"given":"Alex","family":"Prole\u00f3n","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n Toxinas de Origen Animal y sus Antivenenos (TOXIVEN), Laboratorio de Biolog\u00eda Molecular, Facultad de Ciencias Biol\u00f3gicas, Universidad Nacional Mayor de San Marcos, Av. Venezuela Cdra. 34 S\/N, Ciudad Universitaria, Lima 15081, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Ot\u00e1rola","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n Toxinas de Origen Animal y sus Antivenenos (TOXIVEN), Laboratorio de Biolog\u00eda Molecular, Facultad de Ciencias Biol\u00f3gicas, Universidad Nacional Mayor de San Marcos, Av. Venezuela Cdra. 34 S\/N, Ciudad Universitaria, Lima 15081, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2634-1631","authenticated-orcid":false,"given":"Fanny","family":"Lazo","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n Toxinas de Origen Animal y sus Antivenenos (TOXIVEN), Laboratorio de Biolog\u00eda Molecular, Facultad de Ciencias Biol\u00f3gicas, Universidad Nacional Mayor de San Marcos, Av. Venezuela Cdra. 34 S\/N, Ciudad Universitaria, Lima 15081, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6870-9778","authenticated-orcid":false,"given":"Edith","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n Toxinas de Origen Animal y sus Antivenenos (TOXIVEN), Laboratorio de Biolog\u00eda Molecular, Facultad de Ciencias Biol\u00f3gicas, Universidad Nacional Mayor de San Marcos, Av. Venezuela Cdra. 34 S\/N, Ciudad Universitaria, Lima 15081, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9759-288X","authenticated-orcid":false,"given":"Erasmo","family":"Colona-Vallejos","sequence":"additional","affiliation":[{"name":"MODULANS Research Group, Faculty of Biological Sciences, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7425-7453","authenticated-orcid":false,"given":"Libertad","family":"Alzamora-Gonzales","sequence":"additional","affiliation":[{"name":"MODULANS Research Group, Faculty of Biological Sciences, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6407-5235","authenticated-orcid":false,"given":"Jherson","family":"Cisneros-Gutierrez","sequence":"additional","affiliation":[{"name":"MODULANS Research Group, Faculty of Biological Sciences, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyne","family":"Zarria-Romero","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n de Reproducci\u00f3n, Biolog\u00eda del Desarrollo y Ecotoxicolog\u00eda (BIOTOXIC), Facultad de Ciencias Biol\u00f3gicas, Universidad Nacional Mayor de San Marcos, Av. Venezuela Cdra 34 S\/N, Ciudad Universitaria, Lima 15081, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-923X","authenticated-orcid":false,"given":"Miryam Paola","family":"Alvarez Flores","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Nascimento Gomes","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7002-5180","authenticated-orcid":false,"given":"Thatiana","family":"Corr\u00eaa de Melo","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1437-5607","authenticated-orcid":false,"given":"Ronnie G.","family":"Gavilan","sequence":"additional","affiliation":[{"name":"Centro Nacional de Salud P\u00fablica, Instituto Nacional de Salud-Per\u00fa, Lima 15072, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6112-2584","authenticated-orcid":false,"given":"Javier","family":"C\u00e1rdenas Tenorio","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica, Facultad de Ciencias de la Salud, Universidad Nacional del Callao, Av. 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