ACP transacylase

MALEATE ISOMERASE MALONYL-C0A.ACP TRANSACYLASE MALYL-CoA LYASE... 

The now-vacant ACP accepts a three-carbon malonate unit from malonyl CoA. Domain Malonyl CoA-ACP-transacylase. 

Fatty acid synthesis begins when the substrates, acetyl-CoA and malonyl-CoA, are transferred onto the protein by malonyl-CoA acetyl-CoA-ACP transacylase (MAT, steps 1 and 2 in fig. 18.12a). The numbers in parentheses below the abbreviation of the enzyme in this figure refer to the reactions shown in fig. 18.12. (Whereas E. coli has separate enzymes that catalyze the transfer of acetyl- and malonyl-CoA to ACP, both reactions are catalyzed by the same enzymatic activity (MAT) on the animal fatty acid synthase.) Subsequently, /3-ketobutyryl-ACP and CO2 are formed in a condensation reaction catalyzed by /3-ketoacyl-ACP synthase (KS, step 3 in fig. 18.12a). 

Fig. 4. X-ray determined protein crystal structures of multienzyme ensembly lines, (a) Mammalian fatty acid synthase at 4.5 A resolution (PDB 2cf2). Domain organization A starter substrate, acetyl-CoA or malonyl-CoA, gets loaded onto the acyl-carrler protein (ACP/absent in the structure) via the malonyl-CoA-/acetyl-CoA-ACP transacylase (MAT). Then, the ketoacyl synthase (KS) catalyzes a decarboxylative condensation reaction and forms the B-ketoacyl-ACP. This is followed from a reduction reaction catalyzed by the B-ketoacyl reductase (KR). Subsequently, the Intermediate gets dehydrated by a dehydratase (DH) and additionally reduced by a B-enoyl reductase (ER). The product gets released from the ACP by a thloesterase (absent in the structure), (b) Module 3 of 6-deoxyerthronolide B synthase at 2.6 A resolution (PDB 2qo3) bound to the inhibitor cerulin. The ketosynthase (KS) - acyltransferase (AT) di-domain is part of the large homodimeric polypeptide involved in biosynthesis of erythromycin from Saccharopolyspora erythraea...

The first reaction, catalyzed by Acetyl-CoA ACP transacylase, transfers an acetyl group from Coenzyme A to the cysteinyl-S on ACPi. 

Next, a malonyl-group is transferred from a Coenzyme A to the pantetheinyl-S of ACP2 by Malonyl-CoA ACP transacylase. 

Steps 1-2 of Figure 29.5 Acyl Transfers The starting material for fatty-acid synthesis is the thioester acetyl CoA, the ultimate product of carbohydrate breakdown, as we ll see in Section 29.6. The synthetic pathway begins with several priming reactions, which transport acetyl CoA and convert it into more reactive species. The first priming reaction is a nucleophilic acyl substitution reaction that converts acetyl CoA into acetyd ACP (acyl carrier protein). The reaction is catalyzed by ACP transacylase. 

For the malonate group to be used for fatty acid synthesis, it must first be transferred from malonyl-CoA to malonyl-ACP by the 32.4-kDa monomeric malonyl-CoA ACP transacy-lase, the product of the fabD gene (Fig. 2). A stable malonyl-serine enzyme intermediate is formed during the course of the FabD reaction, and subsequent nucleophilic attack on this ester by the sulfhydryl of ACP yields malonyl-ACP. The high reactivity of the serine in malonyl-ACP transacylase is due to the active site being composed of a nucleophilic elbow as observed in alpha/beta hydrolases. The serine is hydrogen bonded to His-201 in a fashion similar to serine hydrolases. 

The last two carbons of the fatty acid chain (i.e., those most distal from the carboxylate group) are the first introduced into the nascent chain, and acetyl-CoA can be thought of as the primer molecule of fatty acid synthesis in E. coli. The initial condensation reaction, catalyzed by P-ketoacyl-ACP synthase III (FabH), utilizes acetyl-CoA and malonyl-ACP to form the four-carbon acetoacetyl-ACP with concomitant loss of COj (Fig. 2). FabH also possesses acetyl-CoA ACP transacylase activity, and for many years it was thought that acetyl-ACP was the actual primer. However, acetyl-ACP appears to be a product of a side reaction, and the role, if any, played by this intermediate in the pathway is unknown. 

Fig. 2. Initiation of fatty acid synthesis. (1) Malonyl-CoA ACP transacylase (FabD) transfers the malonyl group from CoA to ACP and then (2) (5-ketoacyl-ACP synthase lit (FabH) catalyzes the initial irreversible condensation of malonyl-ACP with acetyl-CoA to form acetoacetyl-ACP.

Malonyl-CoA + ACP <=> Malonyl-ACP + CoASH (catalyzed by Malonyl-CoA-ACP Transacylase)... 

Acetyl-CoA-ACP Transacylase is an enzyme of fatty acid biosynthesis that catalyzes the transfer of acyl carrier protein (ACP) to acetyl-CoA in the reaction below (Figure 18.24). Acetyl-ACP is the initial two carbon unit onto which the initial malonyl-ACP is added to form / -ketoacyl-ACP. 

ACP is covalently linked to acetyl-CoA and malonyl-CoA by the enzymes acetyl-CoA-ACP transacylase and malonyl-CoA-ACP transacylase, respectively. 

The finding of plants with high proportions of molecular species with 16 carbon fatty acids at both sn-1 and sn-2 positions requires a revision of our conclusions regarding the fatty acid specificity of the G-3-P acyl-ACP transacylase. We... 

FabD CoA-ACP transacylase recombinant Escherichia coli et al. (2005), Taguchi et al. (1999)... 

Pathway III involves 3-hydroxyacyI-ACP-CoA transferase (PhaG) and malonyl-CoA-ACP transacylase (FabD), which help supply 3-hydroxyacyl-ACP to form PHA monomer 3-hydroxyacyI-CoA, leading to PHA formation under the action of PHA synthase (Sudesh et al. 2000 Zheng et al. 2005 Taguchi et al. 1999). 

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