Cloning and heterologous expression of the Trypanosoma brucei lanosterol synthase gene

• Published in: Molecular and biochemical parasitology Vol. 110; no. 2; pp. 399 - 403
• Main Authors: Buckner, Frederick S., Nguyen, Lisa N., Joubert, Bridget M., Matsuda, Seiichi P.T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2000
• Subjects: Animals; Blotting, Southern; Chromosomes, Artificial, Bacterial; Cloning, Molecular; ergosterol; Intramolecular Transferases - chemistry; Intramolecular Transferases - genetics; Intramolecular Transferases - metabolism; Lanosterol - biosynthesis; Lanosterol synthase; Molecular Sequence Data; Oxidosqualene cyclase; Sterol; Sterol biosynthesis; Sterols; Trypanosoma brucei; Trypanosoma brucei brucei - enzymology; Trypanosoma brucei brucei - genetics; Yeasts - enzymology; Yeasts - genetics; Sterol biosynthesis; kb, kilobases; OSC, oxidosqualene cyclase; ORF, open reading frame; PCR, polymerase chain reaction; RACE, rapid amplification of cDNA ends; BAC, bacterial artificial chromosome; Oxidosqualene cyclase; Trypanosoma brucei; Lanosterol synthase
• ISSN: 0166-6851; 1872-9428
• DOI: 10.1016/S0166-6851(00)00267-X

Sterols are essential components of eukaryotic membranes. Procyclic forms of Trypanosoma brucei synthesize ergosterol, the same sterol that is found in fungi. Trypanosoma cruzi and closely related Leishmania spp. synthesize ergosterol and similar sterols in all their various life cycle stages. Whereas sterol biosynthesis is one of the most thoroughly studied biochemical pathways in the model eukaryote, Saccharomyces cerevisiae, very little is known about this pathway in trypanosomatid organisms. For example, in yeast 12 enzymes of the committed sterol biosynthesis pathway (after farnesyl pyrophosphate synthase) have been cloned and extensively characterized; only one has been cloned from one trypanosomatid organism, i.e. the putative squalene synthase of Leishmania major appears as a database entry in GenBank (AF155593). Since sterol biosynthesis is an excellent target for antimicrobial therapy, as demonstrated by the success of sterol biosynthesis inhibitors against fungi, more intensive research of this enzyme pathway is needed in trypanosomatid parasites.