Fungal Enzyme Deconstructed

The antibiotic erythromycin and other products of a ubiquitous family of enzymes known as polyketide synthases are produced in a fundamentally different way in fungi than they are in bacteria. A team led by Craig A. Townsend at Johns Hopkins University has now teased apart the individual functions of each active domain in a fungal polyketide synthase that produces the carcinogen aflatoxin B₁ (shown). Such an accomplishment gives scientists a broad framework with which to understand how fungal enzymes operate (Science 2008, 320, 243). In bacteria, each catalytic domain in polyketide synthases performs a single synthetic operation that leads progressively toward the end product. Fungal polyketide synthases, on the other hand, reuse certain domains in iterations of catalytic cycles. The group "deconstructed"—dissected and reconstituted—the enzyme into seven catalytic domains and examined the functions of each using mass spectrometry to monitor the steps along the reaction pathway.