title: The Methylerythritol Phosphate Pathway to Isoprenoids.
abstract: Isoprenoids constitute one of the most diverse classes of natural products. As a compound class, they are essential to basic metabolic processes including cell-wall biosynthesis, post-translational protein modifications, and signaling. In addition, isoprenoid secondary metabolites are highly valuable natural products with a wide range of biotechnological applications. The biosynthesis of their two universal building blocks, isopentenyl diphosphate and dimethylallyl diphosphate, was thought to proceed exclusively by way of mevalonate as a key intermediate until a novel pathway involving methylerithritol phosphate (MEP) was discovered in the early 1990s. In this review, we describe the seven enzymes of the MEP pathway, along with their discoveries, three-dimensional structures, and mechanisms. The latter include examples of remarkable enzyme catalysis including an unusual cytidilation reaction and the use of iron-sulfur cluster cofactors in reductive ring opening and hydroxy-group elimination. Furthermore, isoprenoid biosynthesis shows a characteristic species distribution. A brief overview highlights the MEP pathway's potential as a selective drug target, which is absent in humans but essential to the survival of many important bacterial and apicomplexan pathogens.
authors.affiliation: Center for Integrated Protein Science Munich (CIPSM) at the Department Chemie, Technische Universität München , Lichtenbergstraße 4, 85748 Garching, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Frank
authors.affiliation: Center for Integrated Protein Science Munich (CIPSM) at the Department Chemie, Technische Universität München , Lichtenbergstraße 4, 85748 Garching, Germany.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0002-1660-340X
authors.initials: M
authors.lastname: Groll
mesh_terms: D002384:Catalysis; D004896:Erythritol / Q000378:metabolism*; D013729:Terpenes / Q000378:metabolism*
chemical_list: D013729:Terpenes; D004896:Erythritol