Cyclopropane mycolic acid synthase (CMAS)

Cyclopropane mycolic acid synthases are S-adenosyl-L-methionine-dependent methyltransferases found in *Mycobacterium tuberculosis* and related bacteria. They catalyze the conversion of double bonds in mycolic acid precursors to cyclopropane rings, a critical modification that impacts cell wall impermeability, resistance to antibiotics, immunomodulation, and bacterial persistence. There are multiple CMAS enzymes (e.g., CmaA1, CmaA2, CmaA3/PcaA), each with specific substrate selectivity, responsible for distinct cyclopropanation patterns in mycolic acids. These enzymes are essential for virulence and survival in host environments, making them validated drug targets for novel tuberculosis therapies.

Other names

Cyclopropane fatty acid synthaseCyclopropane-fatty-acyl-phospholipid synthaseMycolic acid methyltransferaseS-adenosylmethionine-dependent methyltransferaseSAM-MTCFA synthaseAdoMet-MTMA-MTcmaA1CmaA2CmaA3PcaA

Inhibitors would block the methyltransferase-catalyzed cyclopropanation of mycolic acids, thereby disrupting cell wall synthesis and bacterial survival. The enzymatic mechanism involves methyl transfer from S-adenosyl-L-methionine (SAM) to a substrate double bond, catalyzing cyclopropane ring formation.