In enzymology, an erythronolide synthase (also 6-Deoxyerythronolide B Synthase or DEBS) is an enzyme that catalyzes the chemical reaction 6 malonyl-CoA + propanoyl-CoA 7 CoA + 6-deoxyerythronolide B Thus, the two substrates of this enzyme are malonyl-CoA and propanoyl-CoA, whereas its two products are CoA and 6-deoxyerythronolide b. This enzyme participates in biosynthesis of 12-, 14- and 16-membered macrolides. This enzyme belongs to the family of transferases, it has been identified as part of a Type 1 polyketide synthase module. DEBS is found in Saccharopolyspora erythraea and other actinobacteria, and is responsible for the synthesis of the macrolide ring which is the precursor of the antibiotic erythromycin. There have been three categories of polyketide synthases identified to date, type 1, 2 and 3. Type one synthases involve large multidomain proteins containing all the sites necessary for polyketide synthesis. Type two synthases contain active sites distributed among several smaller polypeptides, and type three synthases are large multi-protein complexes containing modules which have a single active site for each and every step of polyketide synthesis. In the case of DEBS, there are three large multi-functional proteins, DEBS 1,2, and 3, that each exist as a dimer of two modules. Each module consists of a minimum of a Ketosynthase (KS), Acyl carrier protein (ACP) site, and acyltransferase (AT), but may also contain a Ketoreductase (KR), Dehydrotase (DH), and Enol Reductase (ER) for additional reduction reactions. The DEBS complex also contains a Loading Domain on module 1 consisting of an acyl carrier protein and an acyltransferase. The terminal Thioesterase acts solely to terminate DEBS polyketide synthesis and cyclize the macrolide ring. Module components and functions Essential components Ketosynthase The active site of this enzyme has a very broad specificity, which allows for the synthesis of long chains of carbon atoms by joining, via a thioester linkage, small organic acids, such as acetic and malonic acid. The KS domain receives the growing polyketide chain from the upstream module and subsequently catalyzes formation of the C-C bond between this substrate and an ACP-bound extender unit that is selected by the AT domain. Acyltransferase Each AT domain has an α-carboxylated CoA thioester (i.e. methylmalonyl-CoA) This specificity prevents non-essential addition of enzymes within the module. The AT captures a nucleophilic β-carboxyacyl-CoA extender unit and transfers it to the phosphopantetheine arm of the ACP domain. Functions via catalyzing acyl transfer from methylmalonyl-CoA to the ACP domain within the same