Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Center for Environmental Sciences, Institute of Humanities, Arts and Sciences, Federal University of Southern Bahia, Porto Seguro, Brazil.
Front Cell Infect Microbiol. 2022 Apr 21;12:869085. doi: 10.3389/fcimb.2022.869085. eCollection 2022.
Malaria is one of the most widespread parasitic diseases, especially in Africa, Southeast Asia and South America. One of the greatest problems for control of the disease is the emergence of drug resistance, which leads to a need for the development of new antimalarial compounds. The biosynthesis of isoprenoids has been investigated as part of a strategy to identify new targets to obtain new antimalarial drugs. Several isoprenoid quinones, including menaquinone-4 (MK-4/vitamin K2), α- and γ-tocopherol and ubiquinone (UQ) homologs UQ-8 and UQ-9, were previously detected in cultures of in asexual stages. Herein, we described for the first time the presence of phylloquinone (PK/vitamin K1) in and discuss the possible origins of this prenylquinone. While our results in metabolic labeling experiments suggest a biosynthesis of PK prenylation phytyl pyrophosphate (phytyl-PP) with phytol being phosphorylated, on the other hand, exogenous PK attenuated atovaquone effects on parasitic growth and respiration, showing that this metabolite can be transported from extracellular environment and that the mitochondrial electron transport system (ETS) of is capable to interact with PK. Although the natural role and origin of PK remains elusive, this work highlights the PK importance in plasmodial metabolism and future studies will be important to elucidate in seeking new targets for antimalarial drugs.
疟疾是最广泛流行的寄生虫病之一,尤其在非洲、东南亚和南美洲。控制这种疾病的最大问题之一是药物耐药性的出现,这导致了开发新的抗疟化合物的需求。异戊二烯类化合物的生物合成已作为确定新靶标以获得新的抗疟药物的策略的一部分进行了研究。几种异戊烯醌,包括menaquinone-4(MK-4/维生素 K2)、α-和γ-生育酚和泛醌(UQ)类似物 UQ-8 和 UQ-9,以前在无性阶段的培养物中被检测到。在此,我们首次描述了 在 和讨论这种类异戊二烯醌的可能来源。虽然我们在代谢标记实验中的结果表明 PK 的生物合成是通过植基焦磷酸(phytyl-PP)与叶绿醇的磷酸化进行的,另一方面,外源性 PK 减弱了阿托伐醌对寄生虫生长和呼吸的作用,表明这种代谢物可以从细胞外环境中运输,并且 的线粒体电子传递系统(ETS)能够与 PK 相互作用。尽管 PK 的自然作用和来源仍然难以捉摸,但这项工作强调了 PK 在疟原虫代谢中的重要性,未来的研究对于阐明寻找抗疟药物的新靶标将是重要的。