Biochemical and molecular studies of a putative mitochondrial Nicotinamide Nucleotide Transhydrogenase (NNT) from Aspergillus fumigatus

• Grant number: 22/11677-0
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2023
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Sergio Akira Uyemura
• Grantee: Sergio Akira Uyemura
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Aspergillus fumigatus is a saprophytic fungus that has been found in all regions of the world. It is believed that the natural ecological niche is the soil, where it survives and grows on decaying vegetables. In recent years, the fungus A. fumigatus has gone from being just a minor saprophytic fungus to becoming one of the main opportunistic pathogens in immunosuppressed patients.In the last 30 years, the bioenergetics and molecular biology laboratory has studied the mitochondrial energy metabolism of the saprophytic fungus A. fumigatus. Since the last project entitled "Bioenergetic and molecular studies of a mitochondrial NAD+/NADH transporter from Aspergillus fumigatus" we have focused our studies to understand the regulation of the mitochondrial content of NAD+/NADH, which has been attributed as a form of resistance of these microorganisms under hostile conditions. Recently, through bioinformatics analysis, in the genome sequence of A. fumigatus it was possible to find a putative sequence of the nicotinamide nucleotide transhydrogenase gene. This enzyme is present in the plasma membrane of most prokaryotes and in the inner mitochondrial membrane of eukaryotes, including humans. In mammals and microorganisms, this enzyme catalyzes the direct transfer of the hydride ion between NADH and NAD(P)H, the latter cofactor being extremely important in antioxidant defense. Very little is known about its exact function in A. fumigatus. Thus, the objective of this project is to clone, sequence and obtain a knockout of the putative nicotinamide nucleotide transhydrogenase gene from A. fumigatus. (AU)