Discovery and biological characterization of a novel mesoionic insecticide fenmezoditiaz.

BACKGROUND: Many piercing-sucking insects have developed resistance or cross-resistance to many insecticides targeting insect neural nicotinic acetylcholine receptor (nAChR). Here we are aiming to present the discovery of a novel mesoionic insecticide, fenmezoditiaz, by BASF through structure-based drug design (SBDD) approaches. It has recently been added to the Insecticide Resistance Action Committee mode of classification (IRAC 4E). It is being developed for plant protection against piercing-sucking pests, especially rice hopper complex. RESULTS: The soluble acetylcholine binding protein (AChBP) from the sea slug Aplysia californica was modified using site-directed mutagenesis and based on putative aphid nAChR subunit sequences to create soluble insect-like AChBPs. Among them, insect-like ß1 AChBP and native aphid membrane preparation showed the highest correlated biochemical affinity toward structurally diverse ligands. This mutant AChBP was used to understand how insect nAChRs structurally interact with mesoionics, which was then utilized to design novel mesoionics including fenmezoditiaz. It is an excellent systemic insecticide with diverse application methods and has a broad insecticidal spectrum, especially against piercing/sucking insects. It lacks cross-resistance for neonicotinoid resistant plant hoppers. Field-collected brown plant hopper populations from Asian countries showed high susceptibility. CONCLUSIONS: Fenmezoditiaz is a systemic insecticide with a broad spectrum, lack of cross-resistance and it could be an additional tool for integrated pest management and insecticide resistance management, especially for the rice hopper complex. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus calidoustus.

Filamentous fungi produce a wide range of natural products that are commonly used in various industrial contexts (e.g., pharmaceuticals and insecticides). Meroterpenoids are natural products of interest because of their various biological activities. Among the meroterpenoids, there is a group of insecticidal compounds known as the austinoids. These compounds have also been studied because of their intriguing spiro-lactone ring formation along with various modifications. Here, we present an extension of the original austinol/dehydroaustinol biosynthesis pathway from Aspergillus nidulans in the recently identified filamentous fungus Aspergillus calidoustus. Besides the discovery and elucidation of further derivatives, genome mining led to the discovery of new putative biosynthetic genes. The genes involved in the biosynthesis of later austinoid products were characterized, and among them was a second polyketide synthase gene in the A. calidoustus cluster that was unusual because it was a noninterative polyketide synthase producing a diketide. This diketide product was then loaded onto the austinoid backbone, resulting in a new insecticidal derivative, calidodehydroaustin.

Screening of Panamanian Plant Extracts for Pesticidal Properties and HPLC-Based Identification of Active Compounds.

A library of 600 taxonomically diverse Panamanian plant extracts was screened for fungicidal, insecticidal, and herbicidal activities. A total of 19 active extracts were submitted to HPLC-based activity profiling, and extracts of Bocconia frutescens, Miconia affinis, Myrcia splendens, Combretum aff. laxum, and Erythroxylum macrophyllum were selected for the isolation of compounds. Chelerythrine (2), macarpine (3), dihydrosanguinarine (5), and arjunolic acid (8) showed moderate-to-good fungicidal activity. Myricetin-3-O-(6''-O-galloyl)-ß-galactopyranoside (13) showed moderate insecticidal activity, but no compound with herbicidal activity was identified.