An ABC transporter of the ABCC subfamily localized at the plasma membrane confers glyphosate resistance

Synthetic herbicides have been used widely for more than 70 y and have substantially contributed to the efficiency of agriculture. Glyphosate [ N -(phosphonomethyl)glycine] was marketed in 1974 under the trade name Roundup and has become the most used herbicide worldwide. It is a postemergence, nonselective herbicide of low toxicity to animals and humans. While its metabolism in plants is limited, its breakdown in the soil is relatively fast (1). The slow action of glyphosate is related to the fact that it needs to be transported to meristematic areas to become effective. The observation that plants treated with glyphosate accumulate large amounts of shikimate led to the discovery that glyphosate inhibits the 5-enolpyruvyl-shikimate-3 phosphate synthase (EPSPS), an enzyme of the shikimate pathway, which in plants resides in the plastid (Fig. 1) (2). EPSP is converted to chorismate, which is a central metabolite in the synthesis of the three aromatic amino acids. For more than 20 y after its introduction no notable resistance to glyphosate was observed in weeds. In 1996, a transgenic glyphosate-tolerant soybean (Roundup Ready) was introduced, which carried a bacterial gene coding for a glyphosate-insensitive form of EPSPS. Other Roundup Ready major crop plants soon followed, leading to an enormous increase in the application of the herbicide (1, 3). This has raised increasing concern about ground and surface-water pollution and the appearance of residues in food products (4). As a consequence of the increased selective pressure, an increasing number of weeds in fields around the world developed glyphosate resistance (3, 4). Target (EPSPS)-related insensitivity to glyphosate was traced to either mutations in the enzyme or its overproduction by gene amplification or enhanced expression (Fig. 1). The stepwise evolution of mutations (up to three) increased the severity of weed resistance in the field. Other known mechanisms contributing … [↵][1]1To whom correspondence may be addressed. Email: enrico.martinoia{at}uzh.ch. [1]: #xref-corresp-1-1