MalonylCoASynthese

MalonylCoASynthese, more commonly referred to as malonyl-CoA synthetase, is an acyl-CoA ligase that activates malonate to malonyl-CoA. This enzyme provides a route for incorporating malonate-derived two-carbon units into cellular metabolism, distinct from the classical pathway in which acetyl-CoA is carboxylated to form malonyl-CoA in the cytosol.

The catalytic reaction is typically ATP- and CoA-dependent: malonate plus CoA plus ATP is converted to malonyl-CoA, with AMP and pyrophosphate released as byproducts. The mechanism commonly involves formation of a malonyl-adenylate (malonyl-AMP) intermediate followed by nucleophilic attack by CoA on the activated malonate. Mg2+ or other divalent cations commonly support the reaction.

Malonyl-CoA synthetase is found in a range of microorganisms, particularly bacteria, and is frequently encoded within malonate utilization or polyketide biosynthesis gene clusters. In many systems, the gene matB encodes a malonyl-CoA synthetase, sometimes in conjunction with a transporter matC that imports malonate. The enzyme can enable assimilation of environmental malonate and channel it into malonyl-CoA–dependent pathways, including fatty acid elongation and polyketide production.

Biologically, MalonylCoASynthese serves to expand the cellular malonyl-CoA pool from external malonate and to supply extender units for modular biosynthetic systems. Its activity has become a focal point in metabolic engineering aimed at producing malonyl-CoA–derived compounds, and researchers study its substrate range, regulation, and compatibility with heterologous hosts. See also malonyl-CoA, acyl-CoA synthetases, and acetyl-CoA carboxylase.