Regulation of malonyl-CoA metabolism by acyl-acyl carrier protein and beta-ketoacyl-acyl carrier protein synthases in Escherichia coli.
The cessation of phospholipid biosynthesis by the inhibition of the sn-glycerol-3-phosphate acyltransferase using a plsB mutant led to an accumulation of long chain acyl-acyl carrier proteins (acyl-ACP) and the concomitant inhibition of de novo fatty acid biosynthesis in Escherichia coli. Malonyl-CoA did not accumulate when phospholipid and fatty acid synthesis was blocked. However, the inactivation of beta-ketoacyl-ACP synthases I and II with the antibiotic cerulenin triggered a large increase in the accumulation of malonyl-CoA following the cessation of phospholipid synthesis, illustrating that the beta-ketoacyl-ACP synthases were responsible for the degradation of malonyl-CoA in the presence of long chain acyl-ACP. The acyl-ACP requirement for malonyl-CoA degradation activity was confirmed by shifting enoyl-ACP reductase mutants (fabI(Ts)) to the non-permissive temperature, leading to the abrupt cessation of fatty acid synthesis and the accumulation of malonyl-CoA in the absence of cerulenin. Analysis of the ACP pool composition before and after the temperature shift showed that the fabI block did not result in the accumulation of long chain acyl-ACP. These data indicate a feedback regulatory loop that functions to recycle malonyl-CoA to acetyl-CoA following the down-regulation of fatty acid and phospholipid formation and provides a physiological rationale for the acyl-ACP-dependent, malonyl-ACP decarboxylase reaction catalyzed by beta-ketoacyl-ACP synthases I and II.
Heath
R J
RJ
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.
Rock
C O
CO
D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000502:physiology*; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000213:Acyl Carrier Protein / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis
D000213:Acyl Carrier Protein; D005227:Fatty Acids; D010743:Phospholipids; D008316:Malonyl Coenzyme A; D000105:Acetyl Coenzyme A; C077402:3-ketoacyl-acyl carrier protein synthase III; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase