Bioactive C-geranylated metabolites from Piper crassinervium: biological and biosynthetic studies

• Published in: Planta Medica
• Main Authors: López, SN, Lopes, AA, Batista, JMJ, Bolzani, VS, Kato, MJ, Furlan, M
• Format: Conference Proceeding
• Language: English
• Published: 04.08.2008
• ISSN: 0032-0943; 1439-0221
• DOI: 10.1055/s-0028-1084816

Piperaceae family comprises 4 genera and more than 4000 species being the Piper genus the most abundant with approximately 2000 species [1]. Piper crassinervium accumulates antifungal, trypanocidal and antioxidant geranylated metabolites derived from p -hydroquinone and benzoic acid [2,3]. Aromatic geranyltransferases are a group of geranyltransferases that catalyze the C -geranylation step on aromatic substrates; they are membrane-bound enzymes and have showed strict substrate specificity for geranyldiphosphate (GPP) as the prenyl donor, although accept a variety of substrates as acceptors of GPP moieties [4,5]. Here we report the in vivo and in vitro biosynthetic studies carried out to elucidate the biosynthetic origin of geranyl moiety in compounds 1 and 2 . The pattern of incorporation of [1- 13 C]- D -glucose determined by quantitative 13 C NMR spectroscopy indicated that geranyl moiety come from mevalonate and triose/piruvate pathways in compound 1 , but only the triose/piruvate pathway appear involved in compound 2 . In addition, in vitro enzymatic studies of proteic extracts from leaves of P. crassinervium with 4-hydroxy and 3,4-dihydroxy benzoic acids as substrates, showed that O -geranylated products were biosynthesized instead of the C -geranylated ones. Purification and characterization processes of geranyltransferase activity, involving 1D, 2D SDS PAGE and MS studies of microsomal fractions are also discussed. Acknowledgements: State São Paulo Research Foundation (FAPESP), Brazilian National Council for Research (CNPq), São Paulo State University (Unesp) and University of São Paulo (USP). References: 1. Wanke, S. et al. (2007) Molecular Phylogenetics and Evolution 42:477. 2. Lopes, A. et al. Nat. Prod. Res. (submitted). 3. Batista Junior, J. et al. (2008) Biol.Pharm.Bull. 31:538. 4. Kuzuyama, T. et al. (2005) Nature 435:983. 5. Mühlenweg, A. et al. (1998) Planta 205:407.