Characterization of the inhibition of the enzyme alternative oxidase (AOX) by aromatic amides and development of high-throughput screening platform to search for novel inhibitors of the AOX from the fungus Moniliophthora perniciosa

Abstract

Moniliophthora perniciosa is the fungal pathogen that causes the witches' broom disease of cocoa and accounts for a great decline in the production of cocoa beans in Brazil. In spite of M. perniciosa's great economic and social importance, an effective method to control this pathogen is yet to be developed. M. perniciosa withstands one of the most broadly used class of fungicides, strobilurins, fact that was attributed to the existence of the mitochondrial enzyme Alternative Oxidase (MpAox). After a research initiative aimed at developing novel Aox inhibitors suitable for use as agrochemicals, it was found that some molecules such as aromatic amides might fit this purpose. In this regard, the objective of this research project is to explore the role of these aromatic amides as Aox inhibitors, through the employment of biochemical-based assays with purified MpAox. Furthermore, these assays will be adapted to suit High-Throughput Screening requirements, which in turn will bring about the opportunity to screen a large number of compounds in search for novel MpAox inhibitors. (AU)