Methylerythritol Phosphate Pathway for Formation of Isoprene Units

Abstract The carbon skeleton of isoprenoids is derived from the branched C5skeleton of isoprene. Isopentenyl diphosphate and dimethylallyl diphosphate represent the biologic equivalents of isoprene. From research on cholesterol biosynthesis in liver tissues and on ergosterol in yeast, mevalonate was accepted as the universal precursor of isoprenoids. However this assertion is inaccurate. Incorporation of labeled acetate and glucose isotopomers into bacterial isoprenoids and into diterpenes of ginkgo embryos indicated fortuitously the existence of an alternative mevalonate‐independent route. Its full elucidation required experiments using13C‐ and2H‐labeled precursors followed by extensive nuclear magnetic resonance analyses as well as a combination of biochemical and molecular biology methods. These additional studies revealed a complete set of novel unsuspected enzymes.