Pipecolic acid biosynthesis in Rhizoctonia leguminicola. I. The lysine saccharopine, delta 1-piperideine-6-carboxylic acid pathway.
The biosynthesis of pipecolic acid from L-lysine in the fungal parasite, Rhizoctonia leguminicola has been reinvestigated. Pipecolate is then utilized to form the toxic octahydroindolizine alkaloids, slaframine and swainsonine. Incorporation studies of L-versus D-[U-14C]lysine into R. leguminicola metabolites confirmed earlier findings that L-lysine is the predominant substrate for pipecolate formation and D-lysine for alpha-N-acetyllysine (concerned in lysine catabolism). However [alpha-15N]lysine, not [epsilon-15N]lysine as previously reported, labeled pipecolate. Such findings implied that delta 1-piperideine-6-carboxylate, not delta 1-piperideine-2-carboxylate, was formed from lysine and was the immediate precursor of pipecolate. Evidence from cell-free enzyme systems established the following biosynthetic events: L-lysine A----saccharopine B----delta 1-piperideine-6-carboxylate C----pipecolate. Products of reactions A and C were identified from biological and chemical considerations. Reaction B was carried out by a previously undescribed flavin enzyme termed saccharopine oxidase. The product of reaction B, which reacted with p-dimethylaminobenzaldehyde, was reduced with Na-CNB2H3. Its NMR spectrum was identical with that of deuteriated pipecolate prepared from authentic delta 1-piperideine-6-carboxylate, but not from authentic delta 1-piperideine-2-carboxylate. Reaction B represents a branching of primary lysine metabolism from saccharopine to a secondary pathway leading to pipecolate and to octahydroindolizine alkaloids in R. leguminicola.
Wickwire
B M
BM
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Harris
C M
CM
Harris
T M
TM
Broquist
H P
HP
D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D003904:Mitosporic Fungi / Q000378:metabolism*; D010848:Picolinic Acids / Q000378:metabolism*; D010875:Pipecolic Acids / Q000378:metabolism*; D012232:Rhizoctonia / Q000378:metabolism*; D013237:Stereoisomerism
D010848:Picolinic Acids; D010875:Pipecolic Acids; C008919:delta-1-piperidine-6-carboxylic acid; D008239:Lysine; C100169:saccharopine