Genomic Sequence Analysis of Aspergillus fumigatus Lipoxygenase: A Causative Agent of Severe Asthma

Background: Bronchial asthma is an inflammatory disease of the airways which may be worsened due to numerous extrinsic factors. The most common trigger is continuous exposure to allergens of which fungal agents are important factors. There is overwhelming evidence for the presence of fungal sensitization in patients with asthma. It has been proposed that fungal lipoxygenase enzymes and their eicosanoid products are crucial in asthmatic diseases. Human 5-lipoxygenase derived leukotrienes induce inflammation, mucus secretion, vasodilation, and bronchial constriction. Research has also shown that the fungal pathogen Aspergillus fumigatus is capable of secreting LoxB which is a 5-lipoxygenase homolog and it participates in eicosanoid production, including leukotrienes. LoxB is translocated into the lung epithelial cells where it participates in the production of leukotrienes and other eicosanoids, and induces asthmatic responses, such as bronchoconstriction. Analysis from this study gives an idea of facts needed in the structure-based drug design geared towards tackling this disease and this design relies solely on the knowledge of the three-dimensional structure of the biomolecular target which is the lipoxygenase enzyme. Results: In this report, we present a computational analysis of the nucleotide and amino acid composition of lipoxygenase obtained from Aspergillus fumigatus. This in turn was used in the protein secondary and 3D homology modelling necessary for a structure based drug design. The enzyme sensitivity to antifungal drugs was also predicted using results obtained from the protein disordered region analysis. Conclusions: Antifungal drugs designed specifically to target the fungal lipoxygenase tend to act fast based on the enzyme instability. These drugs take advantage of the cytosolic instability of the disulfide bonds which has been analysed also to be of a very minute quantity in the enzyme