Polyketide synthases are enzymes responsible for the biosynthesis of a variety of macrocyclic compounds, some of which are important pharmaceutical agents. The synthases operate in a modular fashion: Each enzyme (or module) is believed to catalyze extension of the chain by one unit and subsequent modifications such as dehydration. Manipulation of the assembly process may lead to more potent pharmaceutical agents.
Olano et al. show that the simple “one extension, one module” rule needs to be revised. In the biosynthesis of the angiogenesis inhibitor and possible antitumor agent borrelidin, one module catalyzes not one but three consecutive rounds of chain extension before passing the intermediate structure to the next module. The authors constructed several mutant enzymes to show that this is not due to insertion of several copies of the module; rather, the same module is used repeatedly. Genetic evidence suggests that such behavior may also occur in other polyketide synthases. — JFU
Chem. Comm. 10.1039/b310648a (2003).