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A sterol biosynthetic pathway in Mycobacterium
D C Lamb1, D E Kelly, N J Manning
1Institute of Biological Sciences, University of Wales Aberystwyth, UK.
FEBS Letters
|November 6, 1998
Summary
Mycobacterium smegmatis synthesizes cholesterol, a sterol previously thought absent in mycobacteria. This discovery opens new avenues for developing chemotherapy agents targeting the sterol biosynthesis pathway in Mycobacterium species.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- Genome sequencing of Mycobacterium tuberculosis and M. leprae revealed homologies to yeast sterol biosynthetic enzymes.
- This suggested a potential sterol biosynthesis pathway in Mycobacterium species, previously uncharacterized.
Purpose of the Study:
- To investigate the presence and activity of a sterol biosynthetic pathway in Mycobacterium smegmatis.
- To confirm cholesterol synthesis and identify pathway intermediates.
Main Methods:
- Culturing Mycobacterium smegmatis.
- Extraction and analysis of non-saponifiable lipids using gas chromatography-mass spectrometry (GC-MS).
- Radiochemical analysis using 14C-radiolabeled mevalonic acid and thin-layer chromatography (TLC).
Main Results:
- Cholesterol was detected in lipid extracts of M. smegmatis.
- Incorporation of 14C-mevalonic acid into a C4-desmethyl sterol co-migrating with authentic cholesterol confirmed de novo sterol synthesis.
- The findings indicate a functional sterol biosynthesis pathway in M. smegmatis.
Conclusions:
- Mycobacterium smegmatis possesses a functional sterol biosynthetic pathway, producing cholesterol.
- This pathway represents a potential target for novel chemotherapy agents against mycobacterial infections.
- Understanding this pathway could lead to new therapeutic strategies for diseases caused by Mycobacterium species.