Glyphosate, a nonselective herbicide and also the world's most widely used herbicide, inhibits 5-enol-pyruvylshikimate-3-phosphate synthase (EPSPS), an enzyme in the aromatic amino acid biosynthetic pathway. Because of its broad-spectrum and potent weed control and favorable environmental characteristics, attempts to engineer glyphosate resistance have been intensive in the past few decades. The use of at least three different mechanisms has conferred glyphosate resistance in normally sensitive crop species. Early work focused on progressive adaptation of cultured plant cells to stepwise increases in glyphosate concentrations. The resulting cells were resistant to glyphosate because of EPSPS overexpression, EPSPS gene amplification, or increased enzyme stability. Further work aimed to achieve resistance by transforming plants with glyphosate metabolism genes. An enzyme from a soil microorganism, glyphosate oxidoreductase (GOX), cleaves the nitrogen– carbon bond in glyphosate yielding aminomethylphosphonic acid. Another metabolism gene, glyphosate N-acetyl transferase (gat), acetylates and deactivates glyphosate. A third mechanism, and the one found in all currently commercial glyphosate-resistant crops, is the insertion of a glyphosate-resistant form of the EPSPS enzyme. Several researchers have used site-directed mutagenesis or amino acid substitutions of EPSPS. However, the most glyphosate-resistant EPSPS enzyme to date has been isolated from Agrobacterium spp. strain CP4 and gives high levels of resistance in planta. Weeds resistant to glyphosate have offered further physiological mechanisms for glyphosate resistance. Resistant field bindweed had higher levels of 3-deoxy-d-arbino-heptulosonate 7-phosphate synthase, the first enzyme in the shikimate pathway, suggesting that increased carbon flow through the shikimate pathway can provide glyphosate resistance. Resistant goosegrass has reduced translocation of glyphosate out of the treated area. Although glyphosate resistance has been achieved by numerous mechanisms, currently the only independent physiological mechanism to give adequate and stable resistance to glyphosate for commercialization of glyphosate-resistant crops has been glyphosate-resistant forms of EPSPS.

Nomenclature: Glyphosate, N-phosphonomethyl glycine; field bindweed, Convolvulus arvensis L.; goosegrass, Eleusine indica L.

Additional index words: EPSPS, gene amplification, glyphosate, glyphosate N-acetyl transferase, glyphosate oxidoreductase, herbicide metabolism, herbicide resistance, shikimate pathway.

Abbreviations: AMPA, aminomethylphosphonic acid; CP4-EPSPS, 5-enol-pyruvylshikimate-3-phosphate synthase isolated from Agrobacterium spp. strain CP4; CTP, chloroplast transit peptide; DAHP synthase, 3-deoxy-d-arabino heptulosonate-7-phosphate synthase; EPSPS, 5-enol-pyruvylshikimate-3-phosphate synthase [E.C. 2.5.1.19]; gat, glyphosate N-acetyl-transferase gene; gox, glyphosate oxidoreductase gene.