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 (14)C-tryptamine has also been demonstrated. dl-2-(13)C-tryptophan specifically enriched two carbon atoms in the (13)C 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-((13)C-methyl) tryptophan was not incorporated into communesins implying that N-methylation of tryptophan is not the first step of the communesin biosynthetic pathway. During deamination of indole-N-((13)C-methyl) tryptophan to 1-(13)C-methylindole-3-carboxylic acid communesin biosynthesis was inhibited. Of several halogenated indoles tested for directed biosynthesis, only dl-6-fluoro-tryptophan and 6-fluoro-tryptamine caused accumulation of the corresponding monofluoro-analogues of communesins A and B.
Wigley
Lucy J
LJ
Department of Biochemistry, Imperial College of Science, Technology and Medicine, South Kensington, London SW7 2AZ, UK.
Mantle
Peter G
PG
Perry
David A
DA
D000470:Alkaloids / Q000096:biosynthesis* / Q000737:chemistry; D018533:Biomass; D005001:Ethionine / Q000494:pharmacology; D005285:Fermentation; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D015394:Molecular Structure; D010407:Penicillium / Q000737:chemistry / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D014364:Tryptophan / Q000378:metabolism
D000470:Alkaloids; D006576:Heterocyclic Compounds, 4 or More Rings; D014364:Tryptophan; D005001:Ethionine