Characterization and inhibitor discovery of one novel malonyl-CoA: Acyl carrier protein transacylase (MCAT) fromHelicobacter pylori

FEBS Letters ◽  
2006 ◽  
Vol 580 (2) ◽  
pp. 697-702 ◽  
Author(s):  
Weizhi Liu ◽  
Cong Han ◽  
Lihong Hu ◽  
Kaixian Chen ◽  
Xu Shen ◽  
...  
Gene ◽  
2013 ◽  
Vol 530 (1) ◽  
pp. 33-38 ◽  
Author(s):  
Jinhu Tian ◽  
Minggang Zheng ◽  
Guanpin Yang ◽  
Li Zheng ◽  
Jiluan Chen ◽  
...  

2011 ◽  
Vol 33 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Sampath Natarajan ◽  
Jin-Kwang Kim ◽  
Tae-Kyun Jung ◽  
Thanh Thi Ngoc Doan ◽  
Ho-Phuong-Thuy Ngo ◽  
...  

1998 ◽  
Vol 180 (17) ◽  
pp. 4596-4602 ◽  
Author(s):  
Satyanarayana Subrahmanyam ◽  
John E. Cronan

ABSTRACT β-Ketoacyl-acyl carrier protein (ACP) synthetase II (KAS II) is one of three Escherichia coli isozymes that catalyze the elongation of growing fatty acid chains by condensation of acyl-ACP with malonyl-ACP. Overexpression of this enzyme has been found to be extremely toxic to E. coli, much more so than overproduction of either of the other KAS isozymes, KAS I or KAS III. The immediate effect of KAS II overproduction is the cessation of phospholipid synthesis, and this inhibition is specifically due to the blockage of fatty acid synthesis. To determine the cause of this inhibition, we examined the intracellular pools of ACP, coenzyme A (CoA), and their acyl thioesters. Although no significant changes were detected in the acyl-ACP pools, the CoA pools were dramatically altered by KAS II overproduction. Malonyl-CoA increased to about 40% of the total cellular CoA pool upon KAS II overproduction from a steady-state level of around 0.5% in the absence of KAS II overproduction. This finding indicated that the conversion of malonyl-CoA to fatty acids had been blocked and could be explained if either the conversion of malonyl-CoA to malonyl-ACP and/or the elongation reactions of fatty acid synthesis had been blocked. Overproduction of malonyl-CoA:ACP transacylase, the enzyme catalyzing the conversion of malonyl-CoA to malonyl-ACP, partially relieved the toxicity of KAS II overproduction, consistent with a model in which high levels of KAS II blocks access of the other KAS isozymes to malonyl-CoA:ACP transacylase.


Author(s):  
Alfred W. Alberts ◽  
Philip W. Majerus ◽  
P. Roy Vagelos

2007 ◽  
Vol 16 (6) ◽  
pp. 1184-1192 ◽  
Author(s):  
Liang Zhang ◽  
Weizhi Liu ◽  
Jianfeng Xiao ◽  
Tiancen Hu ◽  
Jing Chen ◽  
...  

1981 ◽  
Vol 199 (1) ◽  
pp. 221-226 ◽  
Author(s):  
J Sanchez ◽  
J L Harwood

The synthesis of lipids and acyl thioesters was studied in microsomal preparations from germinating pea (Pisum sativum cv. Feltham First) seeds. Under conditions of maximal synthesis (in the presence of exogenous acyl-carrier protein) acyl-acyl-carrier proteins accounted for about half the total incorporation from [14C]malonyl-CoA. Decreasing the concentrations of exogenous acyl-carrier protein lowered the overall synthesis of fatty acids by decreasing, almost exclusively, the radioactivity associated with acyl-acyl-carrier proteins. A time-course experiment showed that acyl-acyl-carrier proteins accumulated most of the radioactive label at the beginning of the incubation but, eventually, the amount of radioactivity in that fraction decreased, while a simultaneous increase in the acyl-CoA and lipid fractions was noticed. Addition of exogenous CoA (1 mM) produced a decrease of total incorporation, but an increase in the radioactivity incorporated into acyl-CoA. The microsomal preparations synthesized saturated fatty acids up to C20, including significant proportions of pentadecanoic acid and heptadecanoic acid. Synthesis of these ‘odd-chain’ fatty acids only took place in the microsomal fraction. In contrast, when the 18,000g supernatant (containing the microsomal and soluble fractions) was incubated with [14C]malonyl-CoA, the radioactive fatty acid and acyl classes closely resembled the patterns produced by germinating in the presence of [14C]acetate in vivo. The results are discussed in relation to the role of acyl thioesters in the biosynthesis of plant lipids.


1975 ◽  
Vol 146 (2) ◽  
pp. 439-445 ◽  
Author(s):  
P J Weaire ◽  
R G O Kekwick

1. The range of fatty acids formed by preparations of ultrasonically ruptured avocado mesocarp plastids was dependent on the substrate. Whereas [1-14C]palmitate and [14C]oleate were the major products obtained from [-14C]acetate and [1-14C]acetyl-CoA, the principal product from [2-14C]malonyl-CoA was [14-C]stearate. 2. Ultracentrifugation of the ruptured plastids at 105000g gave a supernatant that formed mainly stearate from [2-14C]malonyl-CoA and to a lesser extent from [1-14C]acetate. The incorporation of [1-14C]acetate into stearate by this fraction was inhibited by avidin. 3. The 105000g precipitate of the disrupted plastids incorporated [1-14C]acetate into a mixture of fatty acids that contained largely [14C]plamitate and [14C]oleate. The formation of [14C]palmitate and [14C]oleate by disrupted plastids was unaffected by avidin. 4. The soluble fatty acid synthetase was precipitated from the 105000g supernatant in the 35-65%-saturated-(NH4)2SO4 fraction and showed an absolute requirement for acyl-carrier protein. 5. Both fractions synthesized fatty acids de novo.


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