Five Questions about Non-Mevalonate Isoprenoid Biosynthesis

Isoprenoids (also referred to as terpenoids) are the largest group of natural products, comprising over 25,000 known compounds [1]. Each member of this class is assembled from 5-carbon (C5) isoprene units and derived metabolically from the basic building block isopentenyl pyrophosphate (IPP) and its isomer, dimethylallyl pyrophosphate (DMAPP). Subsequent metabolic reactions (such as cyclization) generate enormous complexity and diversity from these basic starting materials. Isoprenoids are vital to all organismal classes, supporting core cellular functions such as aerobic respiration (ubiquinones) and membrane stability (cholesterol) (Figure 1). Isoprenoids also form the largest group of socalled secondary metabolites, such as the extremely diverse classes of plant defensive terpenoids that are widely exploited as perfumes, food additives, and pharmaceutical agents (e.g., the antimalarial compound artemisinin) [2].