RT Journal Article
SR Electronic
T1 A resistance-gene-directed tolerance trait and selective inhibitors proffer HMG-CoA reductase as a new herbicide mode of action
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.18.488698
DO 10.1101/2022.04.18.488698
A1 Joel Haywood
A1 Karen J. Breese
A1 Jingjing Zhang
A1 Mark T. Waters
A1 Charles S. Bond
A1 Keith A. Stubbs
A1 Joshua S. Mylne
YR 2022
UL http://biorxiv.org/content/early/2022/08/02/2022.04.18.488698.abstract
AB Decades of intense herbicide use has led to resistance in weeds. Without innovative weed management practices and new herbicidal modes of action, the unabated rise of herbicide resistance will undoubtedly place further stress upon food security. HMGR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) is the rate limiting enzyme of the eukaryotic mevalonate pathway successfully targeted by statins to treat hypercholesterolemia in humans. As HMGR inhibitors have been shown to be herbicidal, HMGR could represent a new mode of action target for the development of herbicides. Here we present the crystal structure of a HMGR from Arabidopsis thaliana (AtHMG1) which exhibits a wider active site than previously determined structures from different species. This plant conserved feature enabled the rational design of specific HMGR inhibitors, for which we engineered a tolerance trait through sequence analysis of fungal gene clusters. These results suggest HMGR to be a viable herbicide target modifiable to provide a tolerance trait.Competing Interest StatementThe authors have declared no competing interest.