Specialized fatty acid synthesis in African trypanosomes: myristate for GPI anchors.
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.
Morita
Y S
YS
Department of Biological Chemistry, Johns Hopkins Medical School, Baltimore, MD 21205, USA.
Paul
K S
KS
Englund
P T
PT
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002210:Caprylates / Q000378:metabolism; D002474:Cell-Free System; D002569:Cerulenin / Q000494:pharmacology; D003652:Decanoic Acids / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D007848:Laurates / Q000378:metabolism; D009226:Myristates / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology; D013876:Thiophenes / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
D000214:Acyl Coenzyme A; D000900:Anti-Bacterial Agents; D002210:Caprylates; D003652:Decanoic Acids; D005227:Fatty Acids; D017261:Glycosylphosphatidylinositols; D007848:Laurates; D009226:Myristates; D013876:Thiophenes; D002569:Cerulenin; C024343:butyryl-coenzyme A; C031071:decanoic acid; C035068:thiolactomycin; D064429:Fatty Acid Synthases