On the origins of triterpenoid skeletal diversity.

Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches.

In recent years, the impressive development of molecular genetics tools, the sequencing of the Arabidopsis thaliana genome, the availability of DNA or transposon tagged mutants, and the multiple possibilities offered by stable transformation with DNA in sense and antisense orientation have enabled the application of a strategy of gain or loss of function to study the sterol biosynthesis pathway. Here we describe the results obtained with these techniques. The results essentially confirm data obtained previously with sterol biosynthesis inhibitors (SBIs) and enable the precise dissection of biosynthetic pathways. We discuss the advantages and disadvantages of molecular genetics techniques as applied to sterol metabolism. The greater selectivity of these techniques constitutes an invaluable advantage and has led to the discovery of a role for sterols in plant development.

Biosynthesis and accumulation of sterols

There is a close connection between modern-day biosynthesis of particular triterpenoid biomarkers and presence of molecular oxygen in the environment. Thus, the detection of steroid and triterpenoi...

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Steroids, triterpenoids and molecular oxygen

Fatty acid and sterol metabolism: potential antimicrobial targets in apicomplexan and trypanosomatid parasitic protozoa

Steric bulk at position 454 in Saccharomyces cerevisiae lanosterol synthase influences B-ring formation but not deprotonation.

Trypanosome and Animal Lanosterol Synthases Use Different Catalytic Motifs

Small-molecule oxidosqualene cyclase (OSC) inhibitors were found to be effective in assays against cloned OSC-like enzymes from human pathogens. A combinatorial library was prepared and used to identify lead compounds that inhibit the growth of Trypanosoma cruzi, Leishmania mexicana amazonensis, and Pneumocystis carinii in culture. Selectivity for the microorganisms in preference to mammalian cells was observed.

http://uregina.ca/suhdaey/PDF/OSC%20in%20JMC.pdf

Bridget M. Joubert

Papers

Steric bulk at position 454 in Saccharomyces cerevisiae lanosterol synthase influences B-ring formation but not deprotonation.

Trypanosome and Animal Lanosterol Synthases Use Different Catalytic Motifs

Oxidosqualene cyclase inhibitors as antimicrobial agents.

Cloning and heterologous expression of the Trypanosoma brucei lanosterol synthase gene.

Cloning and analysis of Trypanosoma cruzi lanosterol 14α-demethylase