Abstract

A Core Metabolic Enzyme is Responsible for Phosphine Resistance and Fundamental Metabolic Regulation

Horst Joachim Schirra, Research Fellow, The University of Queensland

Phosphine (PH3) is a small redox-active gas that is used to protect global grain reserves, which are threatened by the emergence of PH3 resistance in pest insects. However, little is known about the toxic action of PH3 or the resistance mechanisms. We characterised these mechanisms in C. elegans with NMR-based metabolomics [1]. Combination of metabolomic and genetic data identified dihydrolipoamide dehydrogenase (DLDH) as the enzyme responsible for PH3 resistance. Polymorphisms responsible for genetic resistance cluster around the redox-active catalytic disulfide or the dimerisation interface of DLDH in insects and nematodes. DLDH is a core metabolic enzyme, central to metabolic regulation, and a new class of resistance factor for a redox-active metabolic toxin. It participates in four key steps of core metabolism, which are affected differently by PH3 exposure in mutant and wild-type animals. The position of DLDH in the metabolic network makes it a likely candidate for a central regulator of metabolism. This study is an exceptional case in which a combination of systems biology methods has identified a single genetic cause of phenotypic change that can subsequently be studied with classical methods.