Amended Route To Odd Natural Product

A revised view of how an unusual phosphinic acid-containing natural product is put together has emerged from a study by Neil L. Kelleher, Wilfred A. van der Donk, William W. Metcalf, and coworkers at the University of Illinois, Urbana-Champaign (Nat. Chem. Biol., DOI: 10.1038/nchembio.2007.9). The antibiotic and potent herbicide phosphinothricin tripeptide (PTT, shown) is the only known naturally occurring compound containing a carbon-phosphorus-carbon bond. Nature's route to this compound, which was first isolated in 1972 from Streptomyces bacteria, has therefore been the subject of intense scrutiny. A number of enzymes needed to make PTT have been identified, and armed with this knowledge, the researchers set out to characterize the natural product's complete biosynthetic pathway. By using ³¹P NMR spectroscopy, mass spectrometry, and enzyme mutagenesis, they identified two overlooked intermediates. Their revised route to PTT includes several previously unknown enzyme-catalyzed transformations, including a highly unusual method of carbon-bond cleavage.