An Unusual Carbon-Carbon Bond Cleavage Reaction During Phosphinothricin Biosynthesis

Natural products containing phosphorus-carbon bonds have found widespread use in medicine and agriculture1. One such compound, phosphinothricin tripeptide (PTT), contains the unusual amino acid phosphinothricin (PT) attached to two alanine residues (Fig. 1). Synthetic PT (glufosinate) is a component of two top-selling herbicides (Basta(®) and Liberty(®)), and is widely used with resistant transgenic crops including corn, cotton and canola. Recent genetic and biochemical studies showed that during PTT biosynthesis 2-hydroxyethylphosphonate (HEP) is converted to hydroxymethylphosphonate (HMP) (Fig. 1)2. Reported here are the in vitro reconstitution of this unprecedented C(sp(3))-C(sp(3)) bond cleavage reaction and X-ray crystal structures of the enzyme. The protein is a mononuclear non-heme iron(II)-dependent dioxygenase that converts HEP to HMP and formate. In contrast to most other members of this family, the oxidative consumption of HEP does not require additional cofactors or the input of exogenous electrons. The current study expands the scope of reactions catalyzed by the 2-His-1-carboxylate mononuclear non-heme iron family of enzymes.