Terpene Biosynthesis: Modularity Rules

Terpenes are the largest class of small-molecule natural products on earth, and the most abundant by mass. Here, we summarize recent developments in elucidating the structure and function of the proteins involved in their biosynthesis. There are six main building blocks or modules (a, beta, d, e, and xi) that make up the structures of these enzymes: the aa and ad head-to-tail trans-prenyl transferases that produce trans-isoprenoid diphosphates from C5 precursors; the e head-to-head prenyl transferases that convert these diphosphates into the tri- and tetraterpene precursors of sterols, hopanoids, and carotenoids; the beta di- and triterpene synthases; the xi head-to-tail cis-prenyl transferases that produce the cis-isoprenoid diphosphates involved in bacterial cell wall biosynthesis; and finally the a, a beta, and a beta terpene synthases that produce plant terpenes, with many of these modular enzymes having originated from ancestral a and beta domain proteins. We also review progress in determining the structure and function of the two 4Fe-4S reductases involved in formation of the C5 diphosphates in many bacteria, where again, highly modular structures are found.