On the sequence of bond formation in loline alkaloid biosynthesis

Jerome R. Faulkner, Syed R. Hussaini, Jimmy D. Blankenship, Sitaram Pal, Bruce M. Branan, Robert B. Grossman, Christopher L. Schardl

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Loline alkaloids are saturated pyrrolizidines with an oxygen bridge between carbon atoms C-2 and C-7 and an amino group on C-1. They are bioprotective alkaloids produced by Epichloë and Neotyphodium species, mutualistic fungal endophytes that are symbiotic with cool-season grasses. The sequence of bond formation in loline alkaloid biosynthesis was determined by synthesizing deuterated forms of potential intermediates and feeding them to cultures of the endophyte Neotyphodium uncinatum. These cultures incorporated deuterium from labeled N-(3-amino-3-carboxypropyl)proline and exo-1-aminopyrrotizidine into N-formylloline. The first result suggests that N-(3-amino-3-carboxypropyl) proline is the first committed intermediate in loline biosynthesis, and the second result demonstrates that the pyrrolizidine rings form before the ether bridge. The incorporation of these two compounds into lolines and the lack of incorporation of several related compounds clarify the order of bond formation in loline alkaloid biosynthesis.

Original languageEnglish
Pages (from-to)1078-1088
Number of pages11
JournalChembiochem : a European journal of chemical biology
Issue number7
StatePublished - Jul 2006


  • Alkaloids
  • Biosynthesis
  • Fungal metabolism
  • Heterocycles
  • Natural products
  • Pyrrolizidines

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry


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