Pig and rat liver carnitine palmitoyltransferase I (L-CPTI) share common K(m) values for palmitoyl-CoA and carnitine. However, they differ widely in their sensitivity to malonyl-CoA inhibition. Thus, pig l-CPTI has an IC(50) for malonyl-CoA of 141 nm, while that of rat L-CPTI is 2 microm. Using chimeras between rat L-CPTI and pig L-CPTI, we show that the entire C-terminal region behaves as a si...

Malonyl-CoA is the building block for fatty acid biosynthesis and also a precursor to various pharmaceutically and industrially valuable molecules, such as polyketides and biopolymers. However, intracellular malonyl-CoA is usually maintained at low levels, which poses great challenges to efficient microbial production of malonyl-CoA derived molecules. Inactivation of the malonyl-CoA consumption...

Acyl-malonyl acyl carrier protein (ACP)-condensing enzyme, prepared from extracts of Escherichia coli, catalyzes the condensation of acetyl-ACP and malonyl-ACP to form acetoacetyl-ACP. It also catalyzes the condensation of various longer chain saturated acyl-ACP derivatives with malonyl-ACP to form the P-ketoacyl-ACP of the longer homologues. The enzyme is specific for the acyl-ACP derivatives ...

Lipid metabolism is highly controlled by the nutritional state of the organism. In this study, we identify the mitochondrial sirtuin, SIRT4, as a critical regulator of lipid homeostasis. We find that SIRT4 represses fatty acid oxidation while promoting lipid anabolism. Mechanistically, SIRT4 regulates this balance by inhibiting malonyl-CoA decarboxylase (MCD), an enzyme that produces acetylCoA ...

Malonyl-coenzyme A is an important precursor metabolite for the biosynthesis of polyketides, flavonoids and biofuels. However, malonyl-CoA naturally synthesized in microorganisms is consumed for the production of fatty acids and phospholipids leaving only a small amount available for the production of other metabolic targets in recombinant biosynthesis. Here we present an integrated computation...

There has been considerable interest in the observation that the overt form of carnitine palmitoyltransferase (CPT1) in liver mitochondria is potently inhibited by malonyl CoA [I ,2]. It has been suggested [2] that this is a competitive type of inhibition against long chain acyl CoA substrates. However, this is based upon measurements of ketogenesis [3-51 or indirect calculations of CPT, activi...

The hepatic carnitine palmitoyltransferase that is present on the outer surface of the mitochondrial inner membrane demonstrates hyperbolic substrate saturation curves with oleoyl-CoA in both fasted and fed rats. However, the addition of malonyl-CoA resulted in sigmoid substrate saturation curves, suggesting that malonyl-CoA induced the cooperative behavior. There was more of the outer carnitin...

Malonyl-CoA is the precursor for fatty acid synthesis and elongation. It is also one of the building blocks for the biosynthesis of some phytoalexins, flavonoids, and many malonylated compounds. In plants as well as in animals, malonyl-CoA is almost exclusively derived from acetyl-CoA by acetyl-CoA carboxylase (EC 6.4.1.2). However, previous studies have suggested that malonyl-CoA may also be m...

Malonyl-CoA is the rate-limiting precursor involved in the chain elongation reaction of a range of value-added pharmaceuticals and biofuels. Development of malonyl-CoA responsive sensors holds great promise in overcoming critical pathway limitations and optimizing production titers and yields. By incorporating the Bacillus subtilis trans-regulatory protein FapR and the cis-regulatory element fa...

An intermediate in the fatty acid biosynthetic pathway, malonyl-coenzyme A (CoA), has emerged as a major regulator of energy homeostasis not only in peripheral metabolic tissues but also in regions of the central nervous system that control satiety and energy expenditure. Fluctuations in hypothalamic malonyl-CoA lead to changes in food intake and peripheral energy expenditure in a manner consis...