The M. ulcerans toxins comprise a family of polyketide-derived macrolides, mycolactones, which are formed through condensation of two polyketide chains. Each isolate of M. ulcerans produces a characteristic mixture of mycolactone congeners. M. ulcerans strains from different geographic areas produce distinct patterns of mycolactone congeners. The structural heterogeneity in mycolactones is due to variations in the fatty acid side chain. The structure of the core lactone is invariant.
Genes for mycolactone biosynthesis form a contiguous 110-kb cluster (Fig. 1A) on a large plasmid. The lactone core is encoded by two polyketide synthase (Pks) genes, mlsA1 and mlsA2, and a third polyketide synthase gene, mlsB, encodes the fatty acid side chain. Three accessory genes are found in the mycolactone cluster. One of these, MUP053, encodes a p450 monooxygenase that is thought to produce the hydroxyl at C′-12 on the fatty acid side chain. The gene encoding a FabH-like, type III ketosynthase (KS), located upstream of mlsA1, encodes a putative “joinase” (MUP045), and a small type II thioesterase (TE II) gene (MUP037) is located between mlsA2 and mlsB.
Five categories have been described so far:
Deciphering the genetic basis for polyketide variation among mycobacteria producing mycolactones.(Research article)
Oct 07, 2008; Authors: Sacha J Pidot ; Hui Hong ; Torsten Seemann ; Jessica L Porter ; Marcus J Yip ; Artem Men ; Matthew...