The methyl-branched fortifications of Mycobacterium tuberculosis.
Mycobacterium tuberculosis continues to be the predominant global infectious agent, annually killing over three million people. Recommended drug regimens have the potential to control tuberculosis, but lack of adherence to such regimens has resulted in the emergence of resistant strains. Mycobacterium tuberculosis has an unusual cell envelope, rich in unique long-chain lipids, that provides a very hydrophobic barrier to antibiotic access. Such lipids, however, can be drug targets, as exemplified by the action of the front-line drug isoniazid on mycolic acid biosynthesis. A number of these lipids are potential key virulence factors and their structures are based on very characteristic methyl-branched long-chain acids and alcohols. This review details the history, structure, and genetic aspects of the biosynthesis of these methyl-branched components, good examples of which are the phthiocerols and the mycocerosic and mycolipenic acids.
Minnikin
David E
DE
School of Biosciences, The University of Birmingham, Edgbaston, B15 2TT, Birmingham, United Kingdom. d.e.minnikin@bham.ac.uk
Kremer
Laurent
L
Dover
Lynn G
LG
Besra
Gurdyal S
GS
D002462:Cell Membrane / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D008055:Lipids / Q000096:biosynthesis; D008563:Membrane Lipids / Q000096:biosynthesis*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D009171:Mycolic Acids / Q000378:metabolism; D013329:Structure-Activity Relationship
D005227:Fatty Acids; D008055:Lipids; D008563:Membrane Lipids; D009171:Mycolic Acids; C032992:mycocerosic acid; C008901:phthiocerol dimycocerosate