A sterol biosynthetic pathway in Mycobacterium.
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.
Lamb
D C
DC
Institute of Biological Sciences, University of Wales Aberystwyth, UK.
Kelly
D E
DE
Manning
N J
NJ
Kelly
S L
SL
D002784:Cholesterol / Q000096:biosynthesis; D002849:Chromatography, Gas; D013058:Mass Spectrometry; D008798:Mevalonic Acid / Q000378:metabolism; D020102:Mycobacterium smegmatis / Q000378:metabolism*; D013261:Sterols / Q000096:biosynthesis*
D013261:Sterols; D002784:Cholesterol; D008798:Mevalonic Acid