5-enolpyruvylshikimate-3-phosphate synthase (CP4 EPSPS) (CP4 EPSPS)

5-enolpyruvylshikimate-3-phosphate synthase (CP4 EPSPS) is an enzyme derived from the Agrobacterium sp. strain CP4 that is central to the shikimate pathway. This metabolic pathway is essential for the biosynthesis of aromatic amino acids—phenylalanine, tyrosine, and tryptophan—in plants, bacteria, and fungi, but is absent in humans and other animals (Funke et al., 2006). The CP4 variant of EPSPS is particularly notable for its high catalytic efficiency and its unique structural insensitivity to glyphosate, a broad-spectrum herbicide. In sensitive plants, glyphosate acts as a competitive inhibitor of the native EPSPS enzyme by occupying the binding site intended for phosphoenolpyruvate (PEP), leading to amino acid starvation and plant death (Padgette et al., 1995). Because of its glyphosate-tolerant properties, the gene for CP4 EPSPS has been extensively utilized in agricultural biotechnology to develop herbicide-resistant genetically modified (GM) crops, such as Roundup Ready soybeans and corn. While not a target for human therapeutics, it remains a primary focus in agrochemical research and a potential target for novel antimicrobial development due to its absence in the human proteome.

Other names

AroA5-phosphoshikimate 1-carboxyvinyltransferaseEPSP synthaseEPSPS

Glyphosate acts as a competitive inhibitor of the EPSPS enzyme by mimicking the transition state of phosphoenolpyruvate (PEP), thereby blocking the synthesis of aromatic amino acids. The CP4 variant is uniquely resistant to this inhibition due to structural differences in the active site (Funke et al., 2006).