Molecular basis for resistance against phosphonate antibiotics and herbicides

Abstract

Research in recent years have illuminated data on the mechanisms and targets of phosphonic acid antibiotics and herbicides, including fosfomycin, glyphosate, fosmidomycin and FR900098. Here we review the current state of knowledge of the structural and biochemical characterization of resistance mechanisms against these bioactive natural products. Advances in the understanding of these resistance determinants have spurred knowledge-based campaigns aimed towards the design of derivatives that retain biological activity but are less prone to tolerance.

Identification of the first glyphosate transporter by genomic adaptation

“…In many cases glyphosate resistance is directly linked to the target of the herbicide. As aforementioned, several glyphosate-insensitive EPSP synthase mutant variants have been isolated and engineered (Stalker et al, 1985;Eschenburg et al, 2002;Pollegioni et al, 2011;Sammons and Gaines, 2014;Chekan et al, 2016). Moreover, increased cellular levels of the EPSP synthase due to overexpression of the coding gene or due to gene amplification confers resistance to glyphosate (Figs 7 and 8) Rogers et al, 1983;Gaines et al, 2011;Juglam et al, 2014;Sammons and Gaines, 2014;Dillon et al, 2017).…”

“…The increased cellular levels of the EPSP synthase titrate the glyphosate away and sufficient amounts of aromatic amino acid can be produced. As aforementioned, several glyphosate-insensitive EPSP synthase mutant variants have been isolated and engineered (Stalker et al, 1985;Eschenburg et al, 2002;Pollegioni et al, 2011;Sammons and Gaines, 2014;Chekan et al, 2016). Often, a single amino acid exchange is sufficient to render the EPSP synthase insensitive to glyphosate.…”

“…Inhibition of the EPSP synthase by glyphosate results in depletion of the cellular levels of aromatic amino acids unless they are provided by the growth medium (Gresshoff, 1979;Amrhein et al, 1983;Fischer et al, 1986;Majumder et al, 1995). In the meantime, several glyphosateinsensitive EPSP synthase mutant variants have been generated by either random or directed mutagenesis or they have been isolated from glyphosate-resistant organisms (Stalker et al, 1985;Eschenburg et al, 2002;Kahrizi et al, 2007;Pollegioni et al, 2011;Chekan et al, 2016). In the meantime, several glyphosateinsensitive EPSP synthase mutant variants have been generated by either random or directed mutagenesis or they have been isolated from glyphosate-resistant organisms (Stalker et al, 1985;Eschenburg et al, 2002;Kahrizi et al, 2007;Pollegioni et al, 2011;Chekan et al, 2016).…”

“…Few years after the discovery of the mode of action of glyphosate it has been shown that the aroA gene from enteric bacteria such as Salmonella typhimurium can acquire mutations rendering the encoded EPSP synthase insensitive to glyphosate (Comai et al, 1983). In the meantime, several glyphosateinsensitive EPSP synthase mutant variants have been generated by either random or directed mutagenesis or they have been isolated from glyphosate-resistant organisms (Stalker et al, 1985;Eschenburg et al, 2002;Kahrizi et al, 2007;Pollegioni et al, 2011;Chekan et al, 2016). The structural characterization of the EPSP synthases from Agrobacterium sp.…”

Effect of in vitro glyphosate on Fusarium spp. growth and disease severity in maize

“…As a result of the intensive use of GP products, the residues found both on environmental and plant matrices increased. Glyphosate has a certain resistance to degradation because the C‐P bond is strong . However, this molecule is broken down both in plant tissues and soil by several microorganisms …”