A Single Amino Acid Substitution in One of the Lipases of Aspergillus nidulans Confers Resistance to the Antimycotic Drug Undecanoic Acid

• Published in: Biochemical genetics 2008-10, Vol.46 (9-10), p.557-565
• Main Authors: Brito-Madurro, Ana G., Prade, Rolf A., Madurro, João M., Santos, Mário A., Peres, Nalu T. A., Cursino-Santos, Jeny R., Martinez-Rossi, Nilce M., Rossi, Antonio
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Amino Acids - chemistry; Antifungal Agents - pharmacology; Aspergillus nidulans; Aspergillus nidulans - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Carboxylic Ester Hydrolases - chemistry; Carboxylic Ester Hydrolases - genetics; Catalytic Domain; Cloning; Drug Resistance, Fungal - genetics; Fatty Acids - chemistry; Fatty Acids - pharmacology; Genetic Techniques; Glutamic Acid - chemistry; Human Genetics; Ions; Lipase - chemistry; Lipase - genetics; Lysine - chemistry; Medical Microbiology; Models, Genetic; Molecular Sequence Data; Sequence Homology, Amino Acid; Zoology
• ISSN: 0006-2928; 1573-4927
• DOI: 10.1007/s10528-008-9170-x

A plausible approach to evaluate the inhibitory action of antifungals is through the investigation of the fungal resistance to these drugs. We describe here the molecular cloning and initial characterization of the A. nidulans lipA gene, where mutation ( lipA1 ) conferred resistance to undecanoic acid, the most fungitoxic fatty acid in the C 7:0 –C 18:0 series. The lipA gene codes for a putative lipase with the sequence consensus GVSIS and WIFGGG as the catalytic signature. Comparison of the wild-type and LIP1 mutant strain nucleotide sequences showed a G → A change in lipA1 allele, which results in a Glu 214  → Lys substitution in LipA protein. This ionic charge change in a conserved LipA region, next to its catalytic site, may have altered the catalytic properties of this enzyme resulting in resistance to undecanoic acid.