Lichtenthaler H K, Zeidler J, Schwender J, Müller C
Botanisches Institut II, Universität Karlsruhe, Germany.
Z Naturforsch C J Biosci. 2000 May-Jun;55(5-6):305-13. doi: 10.1515/znc-2000-5-601.
Higher plants and several photosynthetic algae contain the plastidic 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate pathway (DOXP/MEP pathway) for isoprenoid biosynthesis. The first four enzymes and their genes are known of this novel pathway. All of the ca. 10 enzymes of this isoprenoid pathway are potential targets for new classes of herbicides. Since the DOXP/MEP pathway also occurs in several pathogenic bacteria, such as Mycobacterium tuberculosis, and in the malaria parasite Plasmodium falciparum, all inhibitors and potential herbicides of the DOXP/MEP pathway in plants are also potential drugs against pathogenic bacteria and the malaria parasite. Plants with their easily to handle DOXP/MEP-pathway are thus very suitable test-systems also for new drugs against pathogenic bacteria and the malaria parasite as no particular security measures are required. In fact, the antibiotic herbicide fosmidomycin specifically inhibited not only the DOXP reductoisomerase in plants, but also that in bacteria and in the parasite P. falciparum, and cures malaria-infected mice. This is the first successful application of a herbicide of the novel isoprenoid pathway as a possible drug against malaria.
高等植物和几种光合藻类含有用于类异戊二烯生物合成的质体1-脱氧-D-木酮糖5-磷酸/2-C-甲基-D-赤藓糖醇4-磷酸途径(DOXP/MEP途径)。这条新途径的前四种酶及其基因已为人所知。这条类异戊二烯途径的所有约10种酶都是新型除草剂的潜在作用靶点。由于DOXP/MEP途径也存在于几种致病细菌中,如结核分枝杆菌,以及疟原虫恶性疟原虫中,因此植物中DOXP/MEP途径的所有抑制剂和潜在除草剂也是对抗致病细菌和疟原虫的潜在药物。具有易于操作的DOXP/MEP途径的植物因此也是对抗致病细菌和疟原虫的新药的非常合适的测试系统,因为不需要特殊的安全措施。事实上,抗生素除草剂磷霉素不仅能特异性抑制植物中的DOXP还原异构酶,还能抑制细菌和疟原虫恶性疟原虫中的该酶,并能治愈感染疟疾的小鼠。这是新型类异戊二烯途径除草剂作为抗疟疾潜在药物的首次成功应用。