Investigating the specificity of regulators of degradation of hydrocarbons and hydrocarbon-based compounds using structure-activity relationships.

Microbial biosensors which have genes for bioluminescence coupled to genes that control hydrocarbon degradation pathways can be used as reporters on the specificity of regulation of those pathways. Structure-activity relationships can be used to discover what governs that specificity, and can also be used to separate compounds into different groups depending on mode of action. Published data for four different bioluminescent biosensors, reporting on toluene (two separate biosensors), isopropylbenzene, and octane, were analyzed to develop structure-activity relationships between biological response and physical/chemical properties. Good QSARs (quantitative structure-activity relationships) were developed for three out of the four biosensors, with between 88 and 100 per cent of the variance explained. Parameters found to be important in controlling regulator specificity were hydrophobicity, lowest unoccupied molecular orbital energies, and molar volume. For one of the biosensors, it was possible to show that the biological response to chemicals tested fell into three separate classes (non-hydrocarbons, aliphatic hydrocarbons, and aromatic hydrocarbons). A statistically significant QSAR based on hydrophobicity was developed for the fourth biosensor, but was poor in comparison to the other three (44 per cent variance explained).