EC-19. Insidious Intermediates: How a novel detoxifying microbe avoids poisoning itself

Abstract
Human civilization has led to the introduction of vast quantities of synthetic chemicals into nature; these chemicals often lead to detrimental effects to human and animal health and the environment at large. Fortunately, resourceful microorganisms have been shown to evolve the ability to detoxify many different anthropogenic compounds. In one such case, the soil bacterium Sphingobium chlorophenolicum has evolved the ability to degrade pentachlorophenol (PCP), a pesticide that has been outlawed in the US due to its toxicity to humans but is still used in wood treatment. A novel biochemical pathway converts PCP into a harmless cellular metabolite. The first step in the pathway (catalyzed by PCP hydroxylase) generates a highly toxic intermediate, tetrachlorobenzoquinone (TCBQ). We have shown that PCP hydroxylase sequesters TCBQ until it can be reduced by TCBQ reductase to a less-toxic intermediate. We are using enzyme kinetics and protein structural studies to tease out the mechanism for this clever biochemical pathway.