A Novel mechanism of herbicide action through disruption of pyrimidine biosynthesis.

A lead aryl pyrrolidinone anilide identified using high-throughput in vivo screening was optimized for efficacy, crop safety, and weed spectrum, resulting in tetflupyrolimet. Known modes of action were ruled out through in vitro enzyme and in vivo plant-based assays. Genomic sequencing of aryl pyrrolidinone anilide-resistant progeny combined with nutrient reversal experiments and metabolomic analyses confirmed that the molecular target of the chemistry was dihydroorotate dehydrogenase (DHODH), the enzyme that catalyzes the fourth step in the de novo pyrimidine biosynthesis pathway.

Pyrrole-2 carboxamides - A novel class of insect ryanodine receptor activators.

The ryanodine receptor (RyR) is an intracellular calcium channel critical to the regulation of insect muscle contraction and the target site of diamide insecticides such as chlorantraniliprole, cyantraniliprole and flubendiamide. To-date, diamides are the only known class of synthetic molecules with high potency against insect RyRs. Target-based screening of an informer library led to discovery of a novel class of RyR activators, pyrrole-2-carboxamides.

An outlook of FMC's current and future herbicide-resistance management strategies.

Herbicide resistance has emerged globally as a serious threat to profitable crop production. FMC promotes integrated weed management approaches including responsible use of existing herbicides, use of non-herbicide weed control tools, awareness about herbicide resistance issues, and support to herbicide resistance management initiatives. FMC is dedicated to developing sustainable weed control solutions through the discovery of new herbicides with novel sites-of-action, effective formulations, advanced application technology, and proactive monitoring for herbicide resistance.

The impact of a changing atmosphere on chloroplast function, photosynthesis, yield, and food security.

A convergence of global factors is adding to the difficulties of securing a sustainable supply of food and feed to support the increasing global population. The positive impact of the rise in atmospheric CO on photosynthesis is more than offset by the increase in average global temperatures accompanying the change in atmospheric composition. This article provides a brief overview of how these adverse events affect some of the critical molecular processes of the chloroplast and by extension how this impacts the yields of the major crops.

Tubulin modulating antifungal and antiproliferative pyrazinone derivatives.

A novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomyosarcoma cells.

Identification of a critical region in the Drosophila ryanodine receptor that confers sensitivity to diamide insecticides.

Anthranilic diamides, which include the new commercial insecticide, chlorantraniliprole, are an exciting new class of chemistry that target insect ryanodine receptors. These receptors regulate release of stored intracellular calcium and play a critical role in muscle contraction. As with insects, nematodes express ryanodine receptors and are sensitive to the plant alkaloid, ryanodine.

2-Carboxy-D-arabinitol 1-phosphate (CA1P) phosphatase: evidence for a wider role in plant Rubisco regulation.

The genes for CA1Pase (2-carboxy-D-arabinitol-1-bisphosphate phosphatase) from French bean, wheat, Arabidopsis and tobacco were identified and cloned. The deduced protein sequence included an N-terminal motif identical with the PGM (phosphoglycerate mutase) active site sequence [LIVM]-x-R-H-G-[EQ]-x-x-[WN]. The corresponding gene from wheat coded for an enzyme with the properties published for CA1Pase.

Crystal structures of Saccharomyces cerevisiae N-myristoyltransferase with bound myristoyl-CoA and inhibitors reveal the functional roles of the N-terminal region.

Protein N-myristoylation catalyzed by myristoyl-CoA:protein N-myristoyltransferase (NMT) plays an important role in a variety of critical cellular processes and thus is an attractive target for development of antifungal drugs. We report here three crystal structures of Saccharomyces cerevisiae NMT: in binary complex with myristoyl-CoA (MYA) alone and in two ternary complexes involving MYA and two different non-peptidic inhibitors. In all three structures, the majority of the N-terminal region, absent in all previously reported structures, forms a well defined motif that is located in the vicinity of the peptide substrate-binding site and is involved in the binding of MYA.

Analysis of the inhibition of the ergosterol pathway in fungi using the atmospheric solids analysis probe (ASAP) method.

Fungal cells treated with various inhibitors to the ergosterol pathway were analyzed using an Orbitrap mass spectrometer equipped with an atmospheric solids analysis probe (ASAP). The technique is a rapid means for determining which of the multiple steps in the ergosterol pathway were interrupted by an inhibitor. Furthermore, in an inhibitor concentration study, the ASAP method was able to rapidly provide an estimate of the effectiveness of inhibition.

A novel class of inhibitors of peptide deformylase discovered through high-throughput screening and virtual ligand screening.

Peptide deformylase (PDF) has been identified as a promising antibacterial and herbicide target. A structurally novel class of inhibitors containing a 2-thioxo-thiazolidin-4-one heterocycle substituted by an arylidene group at the 5-position and a hexanoic acid side chain at the 3-position was discovered independently via high-throughput screening and virtual ligand screening. Data mining and analogue synthesis established a structure--activity relationship for the side chain region that is consistent with the docked structure.