Unusual "Head-to-Torso" Coupling of Terpene Precursors as a New Strategy for the Structural Diversification of Natural Products.

Abstract

Abstract Terpenoids are ubiquitous in nature and exhibit an immense structural diversity. Commonly, terpenoid biosynthesis involves prenyl diphosphate synthases (terpene synthases) that produce linear prenyl diphosphates with various chain lengths via conventional “head-to-tail” coupling of C5 units. Structural diversification, in contrast, is often mediated by terpene cyclases and additional tailoring enzymes. Recently, however, a few unusual prenyl diphosphate synthases were reported that catalyze noncanonical “head-to-torso” coupling reactions and thus formation of various branched prenyl diphosphates such as isosesquilavandulyl diphosphate. Here, I describe these enzymes in detail and illustrate how these branching reactions are key to formation of various structurally distinct natural products such as the complex polycyclic merochlorin antibiotics from a marine bacterium.