FIGURE 1.  TE cyclization and inhibition.

(a) A polyketide chain linked via a thioester to an acyl carrier protein (ACP) is cyclized to a macrolactone by a TE domain. Substitution of the thioester linkage with a diphenylphosphonate yields an irreversible enzyme inhibitor. The enone of the polyketide substrate is in green. (b) Inhibitor in the active site of the TE domain, pictured with the active site catalytic triad (red), hydrophilic barrier (blue) and potential anchoring residue (green).