Specialized fatty acid synthesis in African trypanosomes: Myristate for GPI anchors

被引:99
作者
Morita, YS [1 ]
Paul, KS [1 ]
Englund, PT [1 ]
机构
[1] Johns Hopkins Med Sch, Dept Biol Chem, Baltimore, MD 21205 USA
关键词
D O I
10.1126/science.288.5463.140
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
African trypanosomes, the cause of sleeping sickness, need massive amounts of myristate to remodel glycosyl phosphatidylinositol (GPI) anchors on their surface glycoproteins. However, it has been believed that the parasite is unable to synthesize any fatty acids, and myristate is not abundant in the hosts' bloodstreams. Thus, it has been unclear how trypanosomes meet their myristate requirement. Here we found that they could indeed synthesize fatty acids. The synthetic pathway was unique in that the major product, myristate, was preferentially incorporated into GPIs and not into other lipids. The antibiotic thiolactomycin inhibited myristate synthesis and killed the parasite, making this pathway a potential chemotherapeutic target.
引用
收藏
页码:140 / 143
页数:4
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