Phosphonate-based enzyme inhibitors

Phosphonates are very stable natural products, synthesized by varied forms of microorganisms. In some - especially marine - ecosystems they make up to 25% of the total bioavailable phosphorus and are therefore important alternative P-sources for microbes. Over the past decade, scientists were able to show that the breakdown of phosphonates in the upper ocean zones contributes significantly to a net flux of greenhouse gases (methane and ethylene) to the atmosphere. Despite their environmental importance, the role of phosphonates for global P- cycling and the effects of the latter on C- and N-cycling are still poorly understood. Still, a broad variety of natural and synthetic phosphonates is used as drugs with antiviral, antibiotic, fungicidal or herbicidal activities, some of which are released into the environment in huge quantities. The herbicide glyphosate is certainly the single most important phosphonate in this regard. Additionally, bulk quantities of phosphonates are used as cleaning-, or washing detergents in household products and industrial processes or as antiscalants. Because of their widespread use, today phosphonates and their breakdown products can be found in the ground and in water bodies over large parts of the planet. A more detailed understanding of phosphonate cycling and of the responsible enzymes is thus of great interest for the development of new, improved drugs, as well as for environmental risk assessment of already used compounds. It will further help to draw a complete picture of the biogeochemical phosphorus cycle. The current project will thus focus on the chemical synthesis of phosphonates which can be either used to study the biochemical processes involved in phosphonate biosynthesis and degradation or could potentially become new phosphonate-based drugs.