Portal de Periódicos da CAPES

Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis

1999; Elsevier BV; Volume: 52; Issue: 5 Linguagem: Inglês

10.1016/s0031-9422(99)00206-x

1873-3700

Harro J. Bouwmeester, T. Eelco Wallaart, Michiel H. A. Janssen, Bert van Loo, B. J. M. JANSEN, Maarten A. Posthumus, Claus O. Schmidt, Jan-Willem de Kraker, Wilfried Α. König, Maurice C. R. Franssen,

Pharmacological Effects of Natural Compounds

The endoperoxide sesquiterpene lactone artemisinin and its derivatives are a promising new group of drugs against malaria. Artemisinin is a constituent of the annual herb Artemisia annua L. So far only the later steps in artemisinin biosynthesis — from artemisinic acid — have been elucidated and the expected olefinic sesquiterpene intermediate has never been demonstrated. In pentane extracts of A. annua leaves we detected a sesquiterpene with the mass spectrum of amorpha-4,11-diene. Synthesis of amorpha-4,11-diene from artemisinic acid confirmed the identity. In addition we identified several sesquiterpene synthases of which one of the major activities catalysed the formation of amorpha-4,11-diene from farnesyl diphosphate. This enzyme was partially purified and shows the typical characteristics of sesquiterpene synthases, such as a broad pH optimum around 6.5–7.0, a molecular mass of 56 kDa, and a Km of 0.6 μM. The structure and configuration of amorpha-4,11-diene, its low content in A. annua and the high activity of amorpha-4,11-diene synthase all support that amorpha-4,11-diene is the likely olefinic sesquiterpene intermediate in the biosynthesis of artemisinin.