Malonyl-CoA:Acyl carrier protein transacylase

Malonyl-CoA Acyl carrier protein transacylase (MCAT or FabD) catalyzes the transfer of a malonyl group between coenzyme A and acyl carrier proteins that are the privileged transporters of the FASH system. Although essential, this enzyme is present in excess and does not have a regulatory role in the FASH pathway, which might explain the relative paucity of reported inhibitors [1],... 

C. Oefner, H. Schulz, A. D Arcy, G.E. Dale, Mapping the active site of Escherichia coU malonyl-CoA-acyl carrier protein transacylase (FabD) by protein crystallography. Acta Crystallogr. Sect. D-Biol. Crystallogr. 62,613-618 (2006)... 

Stapleton, S.R. and Jaworskl, J.G. 1982. Malonyl-CoA acyl carrier protein transacylase from spinach. Fed.Proc., 41 1192. 

Fig. 2 Metabolic routes for mcl-PHA biosynthesis. Pseudomonas putida GPol synthesizes PHA through P-oxidation and P. putida KT2440 synthesizes PHA through fatty add de novo synthesis. Special PHA consisting of 4-hydroxyalkanoate, 5- hydroxyalkanoate, or 6-hydroxyalkanoate can be produced by various bacteria when suitable precursors are supplied. 1 acyl-CoA synthetase, 2 acyl-CoA dehydrogenase, 3 enoyl-CoA hydratase, 4 NAD-dependent (5)-3-hydroxyacyl-CoA dehydrogenase, 5 3-ketoacyl-CoA thiolase, 6 (ItFspecific enoyl-CoA hydratase, 7 NADPH-dependent 3-ketoacyl-CoA reducatase, 8 3-hydroxyacyl-CoA epimerase, 9 mcl-PHA polymerase, 10 acetyl-CoA carboxylase, 11 malonyl-CoA-acyl carrier protein (ACP) tiansacylase, 12 3-keto-ACP synthase, 13 3-keto-ACP reductase, 14 3-hydroxyacyl-ACP dehydratase, 15 enoyl-ACP reductase, 16 acyl-ACP thiolase, 17 (l )-3-hydroxyacyl-ACP-CoA transacylase, 18 mcl-PHA polymerase...

Figure 7.7 Common metabolic pathways that are involved in the biosynthesis of PHA in microorganisms. FabC malonyl-CoA acyl carrier protein (ACP) transcylase, FabD malonyl-CoA-ACP transacylase, FabG 3-ketoacyl-CoA reductase, PhaA P-ketothiolase, PhaB NAOH-dependent acetoacetyl-CoA reductase, PhaC polyhydroxyalkanoates synthase, PhaG 3-hydroxyacyl-ACP GoA transferase, PhaJ (R)-enoyl-GoA hydratase and TCA tricarboxylic acid...

European Atomic Energy Community Ethylene-vinyl alcohol Malonyl-CoA acyl carrier protein Malonyl-CoA-ACP transacylase 3-Ketoacyl-CoA reductase... 

After malonyl-CoA synthesis, the remaining steps in fatty acid synthesis occur on fatty acid synthase, which exists as a multienzyme complex. In the initial reactions acetyl-CoA and malonyl-CoA are transferred onto the protein complex by acetyl-CoA transacylase and malonyl-CoA transacylase (step 1 and step 2 in fig. 18.12a). The acceptor for the acetyl and malonyl groups is acyl carrier protein (ACP). ACP also carries all of the intermediates during fatty acid biosynthesis. The prosthetic group that binds these intermediates is... 

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. 

Figure 3.121 Proposed biosynthetic pathway to hypothemycin 362 by Hpm8 and Hpm3. Hpm8 consists of ketosynthase (KS), malonyl-CoA ACP acyltransferase (MAT), dehydratase (DH), core, enoylreductase (ER), ketoreductase (KR), and acyl-carrier protein (ACP) Hpm3 consists of starter-unit ACP transacylase (SAT), KS, MAT, product template (PT), ACP, and thioesterase (TE). Hpm3 can accept a hexaketide starter unit either from 363-Hpm8 via the SAT domain or from 363-SNAC directly.

Figure 7.45 Proposed biosynthetic mechanism for zearalenone. KS, ketosynthase MAT, malonyl-CoA ACP acyltransferase DH, dehydratase ER, enoylreductase KR, ketoreductase ACP, acyl carrier protein SAT, N-terminal region starter-unit-ACP transacylase PT, prodnct template TE, C-terminal thioesterase.

Malonyl-CoA condenses with an acyl carrier protein (ACP). This reaction is catalyzed by malonyl-CoA ACP transacylase, an enzyme that has been purified from several plants (Ohlrogge et al., 1993). ACP is a relatively small heat-stable protein of 9000 molecular weight that occurs in several isoforms (Browse and Somerville, 1991 Lehninger, 1982). Both ACP and coenzyme A have a 4 -phosphopan-tetheine prosthetic group (Ohlrogge et al., 1993). Amino acid sequences for ACP molecules from more than 15 plants, including both monocots and dicots, are available. The... 

The malonyl-coenzyme A then reacts with acyl-carrier protein (ACP), in the presence of malonyl-CoA-ACP transacylase, to give the malonyl-ACP complex. Acetyl-coenzyme A is then coupled with ACP in the presence of acetyl-CoA-ACP transacylase, and this reacts with the malonyl-ACP, the chain length being increased by two carbon atoms to give the butyryl-ACP complex. The reactions involved are shown in Fig. 9.18. 

Figure 4 (A) Coordinated interaction of members of the condensing (KAS) enzyme family results in biosynthesis of fatty acids in E. coli. The genes encoding each KAS as well as major destinations of the fatty acyl products are shown. Lipoic acid is a precursor of the coenzyme lipoamide. Lipid A consists of p-hydroxymyristate linked to saccharides in the cell membrane. PL are the membrane phospholipids. (B) How do KASes interact with one another and the other members of the FAS complex ACP, acyl carrier protein KR, p-ketoacyl-ACP reductase DH, P-hydroxyacyl-ACP dehydrase ER, enoylacyl-ACP reductase MAL TR, malonyl-CoA ACP transacylase TE, thioesterase AC TR acetyl-CoA ACP transacylase whose contribution to fatty acid synthesis is uncertain since the discovery and characterization of KAS III [33,38].

The biosynthesis of fatty acids in plants Is catalysed by a type II, dissociable, fatty acid synthetase (FAS) made up of at least six catalytic polypeptides and a central, acyl carrier protein (ACP). There are three p Ketoacyl-ACP synthetases (KAS) KAS 1, catalysing the initial reaction between acetyl ACP and malonyl ACP KAS 2, catalysing the addition of acetyl ACP to the elongating fatty acid chain and the recently identified KAS 3. A further enzyme implicated in the initiation of FAS is acetyl CoA ACP transacylase (AC AT) [3]. AC AT catalyses the formation of acetyl ACP. KAS 3, however does not utilise acetyl ACP, instead the condensation occurs between malonyl-ACP and acetyl CoA. There has recently been much discussion about the possible roles of KAS 3 and ACAT which appear to have partially overlapping functions KAS 3 activity has been purified to homogeneity from spinach [1] and E. coli [4]. In both the purified enzyme has the ability to load an acetyl group from acetyl CoA, ACAT activity. Purification of ACAT from E. coli has been reported [3], but as this work predates the discovery of KAS 3 it is not clear whether this activity is resolvable from KAS 3. There is still confusion as to whether plants posses distinct ACAT activity since the assays that have been used for both enzymes contain ACP. 

Figure 22.4 A simplified illustration of saturated fatty acid biosynthesis in microalgal chloroplast. ACCase, Acetyl-CoA carboxylase ACP, acyl carrier protein CoA, coenzyme A ENR, enoyl-ACP reductase HD, 3-hydroxyacyl-ACP dehydratase KAR, 3-ketoacyl-ACP reductase KAS, 3-ketoacyl-ACP synthase MAT, malonyl-CoA ACP transacylase.

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