A Paper published recently in Nature contains a little gem of unusual chemistry – the enzymatic cleavage of a carbon-carbon single bond, with a little help from molecular oxygen. There are a few similar reaktions known in Biochemistry, but they all depend on the presence of activating moieties and ready exit groups. Here, not so. The enzyme Hydroxyethylphosphonate dioxygenase (HEPD) cuts a bond between two not-really activated sp3-carbons of hydroxyethylphosphonate, neatly excising one atom and restoring the original hydroxy group at the end of the molecule.
HEPD originates from certain Streptomyces bacteria, who use it in the production of phosphinotricin, a widely used herbicide. In its active center the enzyme contains non-heme-iron. Some clues how the trick works come from isotope studies. For example tests with 18O demonstrated that at one point, one of the two oxygen atoms in the dioxygen is partially exchanged with water. Apparently the O2 gives birth to hydroxide that immediately attacks the substrate. Except when a solvent water molecule is quicker.
According to the authors, the mechanism works roughly like this: The bound oxygen molecule grabs a hydrogen from the substrate, turning HEP into a radical. Radicals, however, are notoriously prone to rearrangement reactions. And that’s what happens here. In the end we get formiate and hydroxymethylphosphonate.
This is a potentially very useful reaction. The enzyme doesn’t need prosthetic groups or strange coenzymes bu just an iron center and oxygen to tinker with aliphatic hydrocarbons. The basic principle – provoking rearrangements within the carbon skeleton by initially creating a radical – may well work with a wide range of substrates. I’m rather sure this will lead to a frenzy of rational enzyme engineering based on HEPD, resulting in biotech applications not far ahead. Stay tuned.