Specific enzyme functionalities of Fusarium oxysporum compared to host plants.

The genus Fusarium contains some of the most studied and important species of plant pathogens that economically affect world agriculture and horticulture. Fusarium spp. are ubiquitous fungi widely distributed in soil, plants as well as in different organic substrates and are also considered as opportunistic human pathogens. The identification of specific enzymes essential to the metabolism of these fungi is expected to provide molecular targets to control the diseases they induce to their hosts. Through applications of traditional techniques of sequence homology comparison by similarity search and Markov modeling, this report describes the characterization of enzymatic functionalities associated to protein targets that could be considered for the control of root rots induced by Fusarium oxysporum. From the analysis of 318 F. graminearum enzymes, we retrieved 30 enzymes that are specific of F. oxysporum compared to 15 species of host plants. By comparing these 30 specific enzymes of F. oxysporum with the genome of Arabidopsis thaliana, Brassica rapa, Glycine max, Jatropha curcas and Ricinus communis, we found 7 key specific enzymes whose inhibition is expected to affect significantly the development of the fungus and 5 specific enzymes that were considered here to be secondary because they are inserted in pathways with alternative routes.

A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs Against Leishmania major.

We present an approach for detecting enzymes that are specific of Leishmania major compared with Homo sapiens and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific for L major compared with H sapiens, only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific of L major and 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with H sapiens. Among the 40 strictly specific enzymes, we identified sterol 24-C-methyltransferase, pyruvate phosphate dikinase, trypanothione synthetase, and RNA-editing ligase as 4 essential enzymes for L major that may serve as targets for drug development.