Biochemical characterization and inhibition of the alternative oxidase enzyme from the fungal phytopathogen Moniliophthora perniciosa

Author(s)

Barsottini, Mario R. O. ^{[1, 2]} ; Copsey, Alice ^[1] ; Young, Luke ^[1] ; Baroni, Renata M. ^[2] ; Cordeiro, Artur T. ^[3] ; Pereira, Goncalo A. G. ^[2] ; Moore, Anthony L. ^[1]

Affiliation

^[1] Univ Sussex, Sch Life Sci, Biochem & Biomed, Brighton BN1 9QG, E Sussex - England

^[2] Univ Estadual Campinas, Inst Biol, Genom & BioEnergy Lab, Campinas - Brazil

^[3] Brazilian Ctr Res Energy & Mat, Brazilian Biosci Natl Lab, Campinas - Brazil

• Document type: Journal article
• Source: COMMUNICATIONS BIOLOGY; v. 3, n. 1 MAY 25 2020.
• Web of Science Citations: 2

Abstract

Moniliophthora perniciosa is a fungal pathogen and causal agent of the witches' broom disease of cocoa, a threat to the chocolate industry and to the economic and social security in cocoa-planting countries. The membrane-bound enzyme alternative oxidase (MpAOX) is crucial for pathogen survival; however a lack of information on the biochemical properties of MpAOX hinders the development of novel fungicides. In this study, we purified and characterised recombinant MpAOX in dose-response assays with activators and inhibitors, followed by a kinetic characterization both in an aqueous environment and in physiologically-relevant proteoliposomes. We present structure-activity relationships of AOX inhibitors such as colletochlorin B and analogues which, aided by an MpAOX structural model, indicates key residues for protein-inhibitor interaction. We also discuss the importance of the correct hydrophobic environment for MpAOX enzymatic activity. We envisage that such results will guide the future development of AOX-targeting antifungal agents against M. perniciosa, an important outcome for the chocolate industry. Barsottini et al. characterize the alternative oxidase (MpAOX), which is crucial for the survival of Moniliophthora perniciosa, a fungal pathogen of cocoa. They identify key residues for the interactions between this enzyme and its inhibitors, guiding the future development of AOX-targeting antifungal agents that would benefit the chocolate industry. (AU)

• FAPESP's process: 17/12852-2 - Testing of novel AOX inhibitors targeted at the cacao pathogen Monoliophthora perniciosa
• Grantee: Mario Ramos de Oliveira Barsottini
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 14/15339-6 - 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
• Grantee: Mario Ramos de Oliveira Barsottini
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/07653-5 - Discovery and development of new compounds aiming to control Moniliophthora perniciosa, the causal agent of Witches' Broom Disease of cocoa, based on the inhibition of the cellular respiration
• Grantee: Gonçalo Amarante Guimarães Pereira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/13319-6 - Identification of MpPR1-I protein ligands and structural and functional analyses of MpPR-1s of Moniliophthora perniciosa in vitro
• Grantee: Renata Moro Baroni
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/10498-4 - Investigation of strategies of adaptation to the pathogenic life style of fungi from the Moniliophthora genus at various levels of biological organizations: species, biotypes, and geographic lineages
• Grantee: Antonio Vargas de Oliveira Figueira
• Support Opportunities: Research Projects - Thematic Grants