Biosynthesis of fosfomycin in pseudomonads reveals an unexpected enzymatic activity in the metallohydrolase superfamily
Max A. Simon, Chayanid Ongpipattanakul, Satish K. Nair, Wilfred A. van der Donk
Abstract
and soil-dwelling streptomycetes. While the streptomycete pathway has recently been fully elucidated, the pseudomonad pathway is still mostly elusive. Through a systematic evaluation of heterologous expression of putative biosynthetic enzymes, we identified the central enzyme responsible for completing the biosynthetic pathway in pseudomonads. The missing transformation involves the oxidative decarboxylation of the intermediate 2-phosphonomethylmalate to a new intermediate, 3-oxo-4-phosphonobutanoate, by PsfC. Crystallographic studies reveal that PsfC unexpectedly belongs to a new class of diiron metalloenzymes that are part of the polymerase and histidinol phosphatase superfamily.