-Ketoacyl-acyl carrier protein (ACP) synthase III (the fabH gene product) condenses acetyl-CoA with malonyl-ACP to initiate fatty acid biosynthesis in the dissociated, type II fatty acid synthase systems typified by Escherichia coli. The accumulation of malonyl-acyl carrier protein (ACP) following the inhibition of a reconstituted fatty acid synthase system by acyl-ACP implicated synthase III (FabH) as a target for acyl-ACP regulation (Heath, R. J., and Rock, C. O.(1996) J. Biol. Chem. 271, 1833-1836); therefore, the FabH protein was purified and its biochemical and regulatory properties examined. FabH exhibited a K of 40 µM for acetyl-CoA and 5 µM for malonyl-ACP. FabH also accepted other acyl-CoAs as primers with the rank order of activity being acetyl-CoA propionyl-CoA butyryl-CoA. FabH utilized neither hexanoyl-CoA nor octanoyl-CoA. Acyl-ACPs suppressed FabH activity, and their potency increased with increasing acyl chain length between 12 and 20 carbon atoms. Nonesterified ACP was not an inhibitor. Acyl-ACP inhibition kinetics were mixed with respect to acetyl-CoA, but were competitive with malonyl-ACP, indicating that acyl-ACPs decrease FabH activity by binding to either the free enzyme or the acyl-enzyme intermediate. These data support the concept that the inhibition of chain initiation at the -ketoacyl-ACP synthase III step contributes to the attenuation of fatty acid biosynthesis by acyl-ACP.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				A. Jerga and C. O. Rock Acyl-Acyl Carrier Protein Regulates Transcription of Fatty Acid Biosynthetic Genes via the FabT Repressor in Streptococcus pneumoniae J. Biol. Chem., June 5, 2009; 284(23): 15364 - 15368. [Abstract] [Full Text] [PDF]

				Y.-M. Zhang and C. O. Rock Transcriptional regulation in bacterial membrane lipid synthesis J. Lipid Res., April 1, 2009; 50(Supplement): S115 - S119. [Abstract] [Full Text] [PDF]

				Y.-M. Zhang and C. O. Rock Thematic Review Series: Glycerolipids. Acyltransferases in bacterial glycerophospholipid synthesis J. Lipid Res., September 1, 2008; 49(9): 1867 - 1874. [Abstract] [Full Text] [PDF]

				D. M. Doughty, K. H. Halsey, C. J. Vieville, L. A. Sayavedra-Soto, D. J. Arp, and P. J. Bottomley Propionate inactivation of butane monooxygenase activity in 'Pseudomonas butanovora': biochemical and physiological implications Microbiology, November 1, 2007; 153(11): 3722 - 3729. [Abstract] [Full Text] [PDF]

				L. Paoletti, Y.-J. Lu, G. E. Schujman, D. de Mendoza, and C. O. Rock Coupling of Fatty Acid and Phospholipid Synthesis in Bacillus subtilis J. Bacteriol., August 15, 2007; 189(16): 5816 - 5824. [Abstract] [Full Text] [PDF]

				D. J. Miller, Y.-M. Zhang, C. O. Rock, and S. W. White Structure of RhlG, an Essential beta-Ketoacyl Reductase in the Rhamnolipid Biosynthetic Pathway of Pseudomonas aeruginosa J. Biol. Chem., June 30, 2006; 281(26): 18025 - 18032. [Abstract] [Full Text] [PDF]

				Y.-M. Zhang, S. W. White, and C. O. Rock Inhibiting Bacterial Fatty Acid Synthesis J. Biol. Chem., June 30, 2006; 281(26): 17541 - 17544. [Abstract] [Full Text] [PDF]

				T. A. Gould, J. Herman, J. Krank, R. C. Murphy, and M. E. A. Churchill Specificity of Acyl-Homoserine Lactone Synthases Examined by Mass Spectrometry J. Bacteriol., January 15, 2006; 188(2): 773 - 783. [Abstract] [Full Text] [PDF]

				A. K. Brown, S. Sridharan, L. Kremer, S. Lindenberg, L. G. Dover, J. C. Sacchettini, and G. S. Besra Probing the Mechanism of the Mycobacterium tuberculosis {beta}-Ketoacyl-Acyl Carrier Protein Synthase III mtFabH: FACTORS INFLUENCING CATALYSIS AND SUBSTRATE SPECIFICITY J. Biol. Chem., September 16, 2005; 280(37): 32539 - 32547. [Abstract] [Full Text] [PDF]

				Y.-J. Lu, S. W. White, and C. O. Rock Domain Swapping between Enterococcus faecalis FabN and FabZ Proteins Localizes the Structural Determinants for Isomerase Activity J. Biol. Chem., August 26, 2005; 280(34): 30342 - 30348. [Abstract] [Full Text] [PDF]

				Y. Li, G. Florova, and K. A. Reynolds Alteration of the Fatty Acid Profile of Streptomyces coelicolor by Replacement of the Initiation Enzyme 3-Ketoacyl Acyl Carrier Protein Synthase III (FabH) J. Bacteriol., June 1, 2005; 187(11): 3795 - 3799. [Abstract] [Full Text] [PDF]

				G. Brader, S. Sjoblom, H. Hyytiainen, K. Sims-Huopaniemi, and E. T. Palva Altering Substrate Chain Length Specificity of an Acylhomoserine Lactone Synthase in Bacterial Communication J. Biol. Chem., March 18, 2005; 280(11): 10403 - 10409. [Abstract] [Full Text] [PDF]

				M. S. Kimber, F. Martin, Y. Lu, S. Houston, M. Vedadi, A. Dharamsi, K. M. Fiebig, M. Schmid, and C. O. Rock The Structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase (FabZ) from Pseudomonas aeruginosa J. Biol. Chem., December 10, 2004; 279(50): 52593 - 52602. [Abstract] [Full Text] [PDF]

				Y.-M. Zhang and C. O. Rock Evaluation of Epigallocatechin Gallate and Related Plant Polyphenols as Inhibitors of the FabG and FabI Reductases of Bacterial Type II Fatty-acid Synthase J. Biol. Chem., July 23, 2004; 279(30): 30994 - 31001. [Abstract] [Full Text] [PDF]

				C.-Y. Lai and J. E. Cronan Isolation and Characterization of {beta}-Ketoacyl-Acyl Carrier Protein Reductase (fabG) Mutants of Escherichia coli and Salmonella enterica Serovar Typhimurium J. Bacteriol., March 15, 2004; 186(6): 1869 - 1878. [Abstract] [Full Text] [PDF]

				E. S. James and J. E. Cronan Expression of Two Escherichia coli Acetyl-CoA Carboxylase Subunits Is Autoregulated J. Biol. Chem., January 23, 2004; 279(4): 2520 - 2527. [Abstract] [Full Text] [PDF]

				Y.-M. Zhang, B. Wu, J. Zheng, and C. O. Rock Key Residues Responsible for Acyl Carrier Protein and {beta}-Ketoacyl-Acyl Carrier Protein Reductase (FabG) Interaction J. Biol. Chem., December 26, 2003; 278(52): 52935 - 52943. [Abstract] [Full Text] [PDF]

				H. Marrakchi, K.-H. Choi, and C. O. Rock A New Mechanism for Anaerobic Unsaturated Fatty Acid Formation in Streptococcus pneumoniae J. Biol. Chem., November 15, 2002; 277(47): 44809 - 44816. [Abstract] [Full Text] [PDF]

				S. Jackowski, Y.-M. Zhang, A. C. Price, S. W. White, and C. O. Rock A Missense Mutation in the fabB ({beta}-Ketoacyl-Acyl Carrier Protein Synthase I) Gene Confers Thiolactomycin Resistance to Escherichia coli Antimicrob. Agents Chemother., May 1, 2002; 46(5): 1246 - 1252. [Abstract] [Full Text] [PDF]

				X. He and K. A. Reynolds Purification, Characterization, and Identification of Novel Inhibitors of the {beta}-Ketoacyl-Acyl Carrier Protein Synthase III (FabH) from Staphylococcus aureus Antimicrob. Agents Chemother., May 1, 2002; 46(5): 1310 - 1318. [Abstract] [Full Text] [PDF]

				G. E. Schujman, K.-H. Choi, S. Altabe, C. O. Rock, and D. de Mendoza Response of Bacillus subtilis to Cerulenin and Acquisition of Resistance J. Bacteriol., May 15, 2001; 183(10): 3032 - 3040. [Abstract] [Full Text]

				M. S. Davis and J. E. Cronan Jr. Inhibition of Escherichia coli Acetyl Coenzyme A Carboxylase by Acyl-Acyl Carrier Protein J. Bacteriol., February 15, 2001; 183(4): 1499 - 1503. [Abstract] [Full Text]

				K.-H. Choi, R. J. Heath, and C. O. Rock beta -Ketoacyl-Acyl Carrier Protein Synthase III (FabH) Is a Determining Factor in Branched-Chain Fatty Acid Biosynthesis J. Bacteriol., January 15, 2000; 182(2): 365 - 370. [Abstract] [Full Text]

				X. Qiu, C. A. Janson, A. K. Konstantinidis, S. Nwagwu, C. Silverman, W. W. Smith, S. Khandekar, J. Lonsdale, and S. S. Abdel-Meguid Crystal Structure of beta -Ketoacyl-Acyl Carrier Protein Synthase III. A KEY CONDENSING ENZYME IN BACTERIAL FATTY ACID BIOSYNTHESIS J. Biol. Chem., December 17, 1999; 274(51): 36465 - 36471. [Abstract] [Full Text] [PDF]

				R. J. Heath, J. R. Rubin, D. R. Holland, E. Zhang, M. E. Snow, and C. O. Rock Mechanism of Triclosan Inhibition of Bacterial Fatty Acid Synthesis J. Biol. Chem., April 16, 1999; 274(16): 11110 - 11114. [Abstract] [Full Text] [PDF]

				L. Han, S. Lobo, and K. A. Reynolds Characterization of beta -Ketoacyl-Acyl Carrier Protein Synthase III from Streptomyces glaucescens and Its Role in Initiation of Fatty Acid Biosynthesis J. Bacteriol., September 1, 1998; 180(17): 4481 - 4486. [Abstract] [Full Text]

				RichardJ. Heath and CharlesO. Rock Roles of the FabA and FabZ beta -Hydroxyacyl-Acyl Carrier Protein Dehydratases in Escherichia coli Fatty Acid Biosynthesis J. Biol. Chem., November 1, 1996; 271(44): 27795 - 27801. [Abstract] [Full Text] [PDF]

				K.-H. Choi, L. Kremer, G. S. Besra, and C. O. Rock Identification and Substrate Specificity of beta -Ketoacyl (Acyl Carrier Protein) Synthase III (mtFabH) from Mycobacterium tuberculosis J. Biol. Chem., September 1, 2000; 275(36): 28201 - 28207. [Abstract] [Full Text] [PDF]

				M. S. Davis, J. Solbiati, and J. E. Cronan Jr. Overproduction of Acetyl-CoA Carboxylase Activity Increases the Rate of Fatty Acid Biosynthesis in Escherichia coli J. Biol. Chem., September 8, 2000; 275(37): 28593 - 28598. [Abstract] [Full Text] [PDF]

				A. C. Price, K.-H. Choi, R. J. Heath, Z. Li, S. W. White, and C. O. Rock Inhibition of beta -Ketoacyl-Acyl Carrier Protein Synthases by Thiolactomycin and Cerulenin. STRUCTURE AND MECHANISM J. Biol. Chem., February 23, 2001; 276(9): 6551 - 6559. [Abstract] [Full Text] [PDF]

				Y.-M. Zhang, M. S. Rao, R. J. Heath, A. C. Price, A. J. Olson, C. O. Rock, and S. W. White Identification and Analysis of the Acyl Carrier Protein (ACP) Docking Site on beta -Ketoacyl-ACP Synthase III J. Biol. Chem., March 9, 2001; 276(11): 8231 - 8238. [Abstract] [Full Text] [PDF]

				S. S. Khandekar, D. R. Gentry, G. S. Van Aller, P. Warren, H. Xiang, C. Silverman, M. L. Doyle, P. A. Chambers, A. K. Konstantinidis, M. Brandt, et al. Identification, Substrate Specificity, and Inhibition of the Streptococcus pneumoniaebeta -Ketoacyl-Acyl Carrier Protein Synthase III (FabH) J. Biol. Chem., August 3, 2001; 276(32): 30024 - 30030. [Abstract] [Full Text] [PDF]