A sterol biosynthetic pathway in Mycobacterium |
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Authors: | DC Lamb DE Kelly NJ Manning SL Kelly |
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Affiliation: | Institute of Biological Sciences, University of Wales Aberystwyth, UK. |
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Abstract: | The genome sequence of Mycobacterium tuberculosis (and also M. leprae) revealed a significant number of homologies to Saccharomyces cerevisiae sterol biosynthetic enzymes. We addressed the hypothesis of a potential sterol biosynthetic pathway existing in Mycobacterium using cultures of Mycobacterum smegmatis. Non-saponifiable lipid extracts subjected to analysis by gas chromatography-mass spectrometry (GC-MS) showed cholesterol was present. Sterol synthesis by M. smegmatis was confirmed using 14C-radiolabelled mevalonic acid and incorporation into C4-desmethyl sterol co-migrating with authentic cholesterol on TLC. The sterol biosynthetic pathway has provided a rich source of targets for commercially important bioactive molecules and such agents represent new opportunities for Mycobacteria chemotherapy. |
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