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Antimalarial mechanism of action of the natural product 9-methoxystrobilurin G.
Shaw, Philip J; Prommana, Parichat; Thongpanchang, Chawanee; Kamchonwongpaisan, Sumalee; Kongkasuriyachai, Darin; Wang, Yan; Zhou, Zhihua; Zhou, Yiqing.
Afiliación
  • Shaw PJ; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand. philip@biotec.or.th.
  • Prommana P; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand. philip@biotec.or.th.
  • Thongpanchang C; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand. philip@biotec.or.th.
  • Kamchonwongpaisan S; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand. philip@biotec.or.th.
  • Kongkasuriyachai D; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand. philip@biotec.or.th.
  • Wang Y; CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, 200032, China.
  • Zhou Z; CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, 200032, China.
  • Zhou Y; CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, 200032, China.
Mol Omics ; 20(9): 584-594, 2024 Oct 28.
Article en En | MEDLINE | ID: mdl-39262389
ABSTRACT
The natural product 9-methoxystrobilurin G (9MG) from Favolaschia spp basidiomycetes is a potent and selective antimalarial. The mechanism of action of 9MG is unknown. We induced 9MG resistance in Plasmodium falciparum 3D7 and Dd2 strains and identified mutations associated with resistance by genome sequencing. All 9MG-resistant clones possessed missense mutations in the cytochrome b (CYTB) gene, a key component of mitochondrial complex III. The mutations map to the quinol oxidation site of CYTB, which is also the target of antimalarials such as atovaquone. In a complementary approach to identify protein targets of 9MG, a photoactivatable derivative of 9MG was synthesized and applied in chemoproteomic-based target profiling. Three components of mitochondrial complex III (QCR7, QCR9, and COX15) were specifically enriched consistent with 9MG targeting CYTB and complex III function in P. falciparum. Inhibition of complex III activity by 9MG was confirmed by ubiquinone cytochrome c reductase assay using P. falciparum extract. The findings from this study may be useful for developing novel antimalarials targeting CYTB.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium falciparum / Complejo III de Transporte de Electrones / Citocromos b / Estrobilurinas / Antimaláricos Límite: Humans Idioma: En Revista: Mol Omics Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium falciparum / Complejo III de Transporte de Electrones / Citocromos b / Estrobilurinas / Antimaláricos Límite: Humans Idioma: En Revista: Mol Omics Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido