Biology subjects

Gendall, A. R.

Publications and source records attributed to Gendall, A. R..

3 recordsLinked to original sources

bioRxiv2022

A dual-target herbicidal inhibitor of lysine biosynthesis

Herbicides with novel modes of action are urgently needed to safeguard global agricultural industries against the damaging effects of herbicide-resistant weeds. We recently developed the first herbicidal inhibitors of lysine biosynthesis, which provided proof-of-concept for a promising novel herbicide target (Soares da Costa et al., 2021). In this study, we expanded upon our understanding of the mode of action of herbicidal lysine biosynthesis inhibitors. We previously postulated that these inhibitors may act as proherbicides (Soares da Costa et al., 2021). Here we show this is not the case. We report an additional mode of action of these inhibitors, through their inhibition of a second lysine biosynthesis enzyme, and investigate the molecular determinants of inhibition. Furthermore, we extend our herbicidal activity analyses to include a weed species of global significance.

biochemistry↗

bioRxiv2021

Towards Novel Herbicide Modes of Action by Inhibiting Lysine Biosynthesis in Plants

Weeds are becoming increasingly resistant to our current herbicides, posing a significant threat to agricultural production. Therefore, new herbicides are urgently needed. In this study, we exploited a novel herbicide target, dihydrodipicolinate synthase (DHDPS), which catalyses the first and rate-limiting step in lysine biosynthesis. Using a high throughput chemical screen, we identified the first class of plant DHDPS inhibitors that have micromolar potency against Arabidopsis thaliana DHDPS isoforms. Employing X-ray crystallography, we determined that this class of inhibitors binds to a novel and unexplored pocket within DHDPS, which is highly conserved across plant species. We also demonstrated that the inhibitors attenuated the germination and growth of A. thaliana seedlings and confirmed their pre-emergence herbicidal activity in soil-grown plants. These results provide proof-of-concept that lysine biosynthesis represents a promising target for the development of herbicides with a novel mode of action to tackle the global rise of herbicide resistant weeds.

biochemistry↗

bioRxiv2018

NHX-type Na+(K+)/H+ antiporter activity is required for endomembrane trafficking and ion homeostasis in Arabidopsis thaliana

The regulation of ion and pH homeostasis of endomembrane organelles is critical for functional protein trafficking, sorting and modification in eukaryotic cells. pH homeostasis is maintained through the activity of vacuolar H+-ATPases (V-ATPases) pumping protons (H+) into the endomembrane lumen, and counter-action by cation/proton exchangers such as the NHX family of Na+(K+)/H+ exchangers. In plants, disturbing V-ATPase activity at the trans-Golgi network/early endosome (TGN/EE) impairs secretory and endocytic trafficking. However, it is unclear if the endosomal NHX-type antiporters NHX5 and NHX6 play functionally similar roles in endomembrane trafficking through maintaining ion and pH homeostasis. Here we show through genetic, pharmacological, and live-cell imaging approaches that double knockout of endosomal isoforms NHX5 and NHX6 results in impairment of endosome motility, protein recycling at the TGN/EE, but not in the secretion of integral membrane proteins. Furthermore, we report that nhx5 nhx6 mutants are partially insensitive to osmotic swelling of TGN/EE induced by the monovalent cation ionophore monensin. Similarly, nhx5 nhx6 cells are unresponsive to late endosomal swelling by the phosphatidylinositol 3/4-kinase inhibitor wortmannin, demonstrating that NHX5 and NHX6 are required for maintaining endosomal cation balance. Lastly, we report that the distal region of the cytosolic tail of NHX6 is required for mediating NHX6 localisation to late endosomes, but does not appear to be essential for NHX6 function.

plant biology↗