Acetoacetyl acyl carrier protein

Acetoacetic ester synthesis, 839—841, 850. See also Ethyl acetoacetate Acetoacetyl acyl carrier protein, 1021 Acetoacetyl coenzyme A, 1021, 1032 Acetone... 

Jackowski S, Murphy CM, Cronan JE, Rock CO. Acetoacetyl-acyl carrier protein synthase. A target for the antibiotic thiolactomycin. J Biol Chem 1989 264(13) 7624-7629. 

When both building block units are m place on the acyl carrier protein carbon-carbon bond formation occurs between the a carbon atom of the malonyl group and the carbonyl carbon of the acetyl group This is shown m step 1 of Figure 26 3 Carbon-carbon bond formation is accompanied by decarboxylation and produces a four carbon acetoacetyl (3 oxobutanoyl) group bound to acyl earner protein... 

The introduction to Section 26.8 pointed out that mevalonic acid is the biosynthetic precursor of isopentenyl pyrophosphate. The early steps in the biosynthesis of mevalonate from three molecules of acetic acid are analogous to those in fatty acid biosynthesis (Section 26.3) except that they do not involve acyl carrier protein. Thus, the reaction of acetyl coenzyme A with malonyl coenzyme A yields a molecule of acetoacetyl coenzyme A. 

Fatty acid synthesis in bacteria and plants is a multistep process. One transformation in the process involves the reduction of the ketone unit in acetoacetyl AGP (94) with the enzyme [3-ketoacyl-ACP reductase and NADPH (91) to give (3-hydroxybutaryl-ACP (96) and NADP" (92). AGP is the acyl carrier protein, and it is bound to the acetoxy unit via a phosphopantetheine group (marked in cyan in 94). 

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...

The malonyl group is transferred onto an acyl carrier protein, and then reacts with the growing fatty acid chain, bound to the central acyl carrier protein of the fatty acid synthase complex. The carbon dioxide that was added to form malonyl CoA is lost in this reaction. For the first cycle of reactions, the central acyl carrier protein carries an acetyl group, and the product of reaction with malonyl CoA is acetoacetyl-ACP in subsequent reaction cycles, it is the growing fatty acid chain that occupies the central ACP, and the product of reaction with malonyl CoA is a ketoacyl-ACP. 

Although it was known that the intermediates of the p-oxidation cycle are channelled towards PHA biosynthesis, only recently the precursor sources were identified. In A. caviae, the p-oxidation intermediate, trans-2-tnoy -CoK is converted to (R)-3-hydroxyacyl-CoA via (R)-specific hydration catalysed by a (R)-specific enoyl-CoA hydratase [122, 123]. Subsequently, Tsuge and co-workers [124] reported the identification of similar enoyl-CoA hydratases in F. aeruginosa. In the latter case, two different enoyl-CoA hydratases with different substrate specificities channelled both SCL and MCL enoyl-CoA towards PHA biosynthesis. In recombinant . coli it was further shown that 3-ketoacyl-CoA intermediates in the p-oxidation cycle can also be channelled towards PHA biosynthesis by a NADPH-dependent 3-ketoacyl-acyl carrier protein (ACP) reductase [125]. A similar pathway was also identified in F. aeruginosa [126]. In addition, it was also reported that the acetoacetyl-CoA reductase (PhaB) of R. eutropha can also carry out the conversion of 3-ketoacyl-CoA intermediates in Pathway II to the corresponding (R)-3-hydroxyacyl-CoA in E. coli [127]. The results clearly indicate that several channelling pathways are available to supply substrates from p-oxidation cycle to the PHA synthase. This explains why it was not possible to obtain mutants that completely lack PHA accumulation ability, unless the mutation occurred in the PHA synthase gene [128]. 

The product of the reaction above, the acetoacetyl derivative of the acyl carrier protein, is the starting point for the biosynthesis of other compounds besides fatty acids. Steroids derive from a sequence of enzyme-catalyzed Claisen-like condensations that produce the branched five-carbon skeleton of 2-methyl-1,3-butadiene (isoprene), the building block of... 

---