4coumarateCoA

4-Coumaroyl-CoA, also known as p-coumaroyl-CoA, is the CoA thioester of p-coumaric acid. It is an activated hydroxycinnamate that serves as a central building block in the phenylpropanoid pathway and as a starter unit for type III polyketide synthases in plants. The formation of 4-coumaroyl-CoA is catalyzed by 4-coumarate-CoA ligase (4CL) in an ATP-dependent reaction: p-coumarate + CoA + ATP → 4-coumaroyl-CoA + AMP + PPi. Several plant 4CL isoforms display tissue-specific expression and substrate flexibility, enabling flux into multiple biosynthetic routes.

In plant metabolism, 4-coumaroyl-CoA feeds into downstream enzymes that generate a wide array of secondary metabolites. It is the substrate for chalcone synthase (CHS), which condenses 4-coumaroyl-CoA with three molecules of malonyl-CoA to form naringenin chalcone, the precursor to diverse flavonoids. It is also utilized by stilbene synthase to produce resveratrol and related stilbenes. Beyond flavonoids and stilbenes, 4-coumaroyl-CoA contributes to lignin and other hydroxycinnamate-derived polymers through metabolic branches that channel activated intermediates toward monolignol biosynthesis.

Occurrence and significance vary among organisms, but 4-coumaroyl-CoA is a key metabolic node in many plants, integrating phenylpropanoid metabolism with the production of flavonoids, lignins, and other hydroxycinnamyl compounds. Because of its central role, 4CL enzymes and the regulation of 4-coumaroyl-CoA formation are common targets in metabolic engineering aimed at modifying plant polyphenol content and composition.