The effect of amphotericin B on yeast growth and the isolation and identification of sterols for protozoan protein X-ray crystallography

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2017-05

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Abstract

In this study the fungicidal activity of the polyene antimycotic, Amphotericin B, which binds to erosterol and the medical azoles clomitazole, and itraconazole, that inhibits ergosterol biosynthesis, were tested against wild type yeast, ERG6 mutant yeast, and the GL7 sterol auxotroph supplemented with ergosterol or cholesterol. Analysis of growth response to the polyene and ergosterol biosynthesis inhibitors revealed ergosterol played multiple physiological roles in yeast. Using the yeast Candida albicans, which typically synthesizes ergosterol, when treated with itraconazole and 25-azalanosterol to block CYP51 activity and sterol methyl transferase activity, respectively, the main sterols recovered from the treated cells were 14-α-methyl zymosterol, lanosterol, 31-nor lanosterol, and obtusifoliol. In collaboration with structural biologist at Vanderbilt Medical School and University of California San Diego Medical School these 14-α-methyl sterols are being evaluated as complexing agents against protozoan CYP51s for determination of their 3-D structure.

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Masters thesis

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