Transferase 4 -phosphopantetheine-protein

Figure 11.2 Biosynthesis of the nine-membered enediynes. Members of this family share a common biosynthetic pathway for the enediyne core intermediate. Domains are shown in circles with abbreviations (KS, ketosynthase AT, acyltransferase KR, ketoreductase DH, dehydratase TE, thioesterase ACP, acyl carrier protein PPT, phosphopantetheine transferase)...

Fig. 3. Phosphopantetheinylation of the acyl carrier protein (AGP) domain of a polyketide synthase. In order to be active, polyketide synthases must be post-translationally modified by a family of enzymes called phosphopantetheine transferases (PPTases). These enzymes transfer the 4 -phospho-pantetheine arm of Coenzyme A to an active site serine residue in the AGP...

From the pH dependence of the reaction, the formation of a thiolate anion can be concluded (80, Figure 1). Both types of synthetases can be expected to have birrding sites for 4 -phosphopantetheine and, presumably, CoA. The possible transfer of acyl or aminoacyl residues to acyl cairier proteins (ACPs) has not been investigated. However, Heaton and Neuhaus (38) have uncovered a tmique mode of D-Ala attachment to tei-choic acids, consisting of a D-Ala adenylate-fcHming enzyme, a D-Ala carrier protein, and a respiective transferase. Both ACP from Eschencfiid colt and cre))tomyces erythreae also accepted the aminoacyl residue. 

Despite the structural diversity of polyketides, the building blocks of these compounds are simple acyl-CoAs, and the biosynthetic logic is closely associated with that of fatty acid synthases (FASs) [9, 10]. In both polyketide and fatty acid biosynthesis, the growing chain is covalently tethered to an acyl carrier protein (ACP) via a phosphopantetheine (PPant) moiety. The PPant chain, derived from CoA, is attached post-translationaUy to a conserved serine residue on the npo-ACP by a phosphopantetheinyl transferase (PPTase), yielding the mature to-ACP (Scheme 1.1) [11,12],... 

---