A single amino acid substitution in one of the lipases of Aspergillus nidulans confers resistance to the antimycotic drug undecanoic acid.
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.
Instituto de Química, Universidade Federal de Uberlândia, Uberlandia, Brazil.
Ana G
AG
Brito-Madurro
Rolf A
RA
Prade
João M
JM
Madurro
Mário A
MA
Santos
Nalu T A
NT
Peres
Jeny R
JR
Cursino-Santos
Nilce M
NM
Martinez-Rossi
Antonio
A
Rossi
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000935:Antifungal Agents / Q000494:pharmacology*; D001233:Aspergillus nidulans / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry / Q000235:genetics*; D020134:Catalytic Domain; D025141:Drug Resistance, Fungal / Q000235:genetics*; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D005821:Genetic Techniques; D018698:Glutamic Acid / Q000737:chemistry; D007477:Ions; D008049:Lipase / Q000737:chemistry / Q000235:genetics*; D008239:Lysine / Q000737:chemistry; D008957:Models, Genetic; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D000596:Amino Acids; D000935:Antifungal Agents; D005227:Fatty Acids; D007477:Ions; C016173:undecanoic acid; D018698:Glutamic Acid; D002265:Carboxylic Ester Hydrolases; C533185:LipA protein, Aspergillus nidulans; D008049:Lipase; D008239:Lysine