-!- The product, 6-deoxyerythronolide B, contains a 14-membered lactone ring and is an intermediate in the biosynthesis of erythromycin antibiotics. -!- Biosynthesis of 6-deoxyerythronolide B requires 28 active sites that are precisely arranged along three large polypeptides, denoted DEBS1, -2 and -3. -!- The polyketide product is synthesized by the processive action of a loading didomain, six extension modules and a terminal thioesterase domain. -!- Each extension module contains a minimum of a ketosynthase (KS), an acyltransferase (AT) and an acyl-carrier protein (ACP). -!- The KS domain both accepts the growing polyketide chain from the previous module and catalyzes the subsequent decarboxylative condensation between this substrate and an ACP-bound methylmalonyl extender unit, introduce by the AT domain. -!- This combined effort gives rise to a new polyketide intermediate that has been extended by two carbon atoms.