Natural and directed biosynthesis of communesin alkaloids

A role for tryptophan, acetate, mevalonate and methionine in the biosynthesis of communesins A and B, novel structurally-related and biologically-active Penicillium metabolites, has been established by isotopic labelling techniques. The incorporation of C-14-trypt- amine has also been demonstrated. DL-2-C-13-tryptophan specifically enriched two carbon atoms in the C-13 NMR spectrum, thereby defining the intra-molecular arrangement of the two tryptophan-derived moieties. Feeding differentially labelled precursors during communesin production showed that tryptophan and methionine are involved early in the biosynthesis and that mevalonate provides an isoprene which is added later. A biosynthetic pathway involving an early precursor based on tryptophan is proposed. Indole-N-(C-13-methyl) tryptophan was not incorporated into communesins implying that N-methylation of tryptophan is not the first step of the communesin biosynthetic pathway. During clearnination of indole-N-(C-13-methyl) tryptophan to 1-C-13-methylindole-3-carboxylic acid communesin biosynthesis was inhibited. Of several halogenated indoles tested for directed biosynthesis, only DL-6-fluoro-tryptophan and 6-fluorotryptamine caused accumulation of the corresponding monofluoro-analogues of communesins A and B. (c) 2005 Elsevier Ltd. All rights reserved.