Biosynthesis of slaframine, (1S,6S,8aS)-1-acetoxy-6-aminooctahydroindolizine, a parasympathomimetic alkaloid of fungal origin. 3. Origin of the pyrrolidine ring.
The phytopathogen Rhizoctonia leguminicola has previously been shown to incorporate pipecolic acid into the piperidine alkaloids 1-acetoxy-6-aminooctahydroindolizine (slaframine) and 3,4,5-trihydroxyoctahydro-1-pyrindine. In the experiments described here, resting cultures of R. leguminicola were incubated with [1-14C]- and [2-14C]malonic acid and with [1-14C]- and [2-2H]acetic acid. Both acids were incorporated into the ring systems of both alkaloids. Mass spectrometric analysis of 2H-enriched slaframine showed that the label resides in the five-membered ring and that the methyl carbon of acetate is joined to the carboxyl carbon of pipecolate. A pipecolate-dependent decarboxylation of [1-14C]malonate was demonstrated in cell-free extracts of R. leguminicola. The results account for previously unattributed carbons in the two alkaloids and suggest the formation of an eight-carbon intermediate common to both alkaloids by acylation of malonate with pipecolic acid.
D000085:Acetates / Q000378:metabolism; D000470:Alkaloids / Q000096:biosynthesis*; D002250:Carbon Radioisotopes; D003903:Deuterium; D007212:Indolizines / Q000096:biosynthesis*; D007553:Isotope Labeling / Q000379:methods; D008314:Malonates / Q000378:metabolism; D013058:Mass Spectrometry; D003904:Mitosporic Fungi / Q000378:metabolism*; D010875:Pipecolic Acids / Q000378:metabolism; D011759:Pyrrolidines / Q000378:metabolism*; D012232:Rhizoctonia / Q000378:metabolism*; D014316:Tritium
D000085:Acetates; D000470:Alkaloids; D002250:Carbon Radioisotopes; D007212:Indolizines; D008314:Malonates; D010875:Pipecolic Acids; D011759:Pyrrolidines; D014316:Tritium; C009275:slaframine; D003903:Deuterium