DuPont Crop Protection has discovered a new class of piperidinyl thiazole isoxazoline fungicides which represent a step change in the control of Oomycete diseases in potato, grapevine and other specialty crops. The commercial compound will have the common name oxathiapiprolin (DuPont� Zorvec� disease control). Preliminary data including exceptional disease control at low use rates, subcellular distribution of the compound, and lack of cross-resistance to commercial compounds in laboratory-generated, piperidinyl thiazole isoxazoline-resistant mutants suggested a novel mode of action. Initial identification of the target protein, the oxysterol-binding protein (OSBP), was determined by a combination of biochemical and molecular genetic techniques. Target candidates were isolated by exposing partially purified Phytophthora capsici extracts to a piperidinyl thiazole isoxazoline ligand coupled to a solid support matrix followed by differential elution with an inactive and then an active ligand. Visual inspection after SDS-PAGE indicated a single band that was unique to the active compound elution and identification of peptides by mass spectrometry revealed that an OSBP was, by far, the most abundant and unique component of the active compound elution. At the same time, whole transcriptome sequencing of wild-type and a piperidinyl thiazole isoxazoline-resistant P.capsici isolate revealed a mutation in the OSBP conferring a G770V amino acid change. Subsequent sequencing of numerous independent resistant mutants revealed the same mutation or other amino acid-changing mutations in the OSB domain of the OSBP. Transformation of P.capsici with a plasmid containing a resistant version of the OSBP conferred resistance to piperidinyl thiazole isoxazolines, confirming the target identification.

Discovery of the target site of oxathiapiprolin (DuPont� Zorvec� disease control)

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.