title: On the sequence of bond formation in loline alkaloid biosynthesis.
abstract: 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-aminopyrrolizidine 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.
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, 40546-0312, USA.
authors.forename: Jerome R
authors.initials: JR
authors.lastname: Faulkner
authors.forename: Syed R
authors.initials: SR
authors.lastname: Hussaini
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Blankenship
authors.forename: Sitaram
authors.initials: S
authors.lastname: Pal
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Branan
authors.forename: Robert B
authors.initials: RB
authors.lastname: Grossman
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Schardl
mesh_terms: D000470:Alkaloids / Q000096:biosynthesis* / Q000737:chemistry; D001203:Ascomycota / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D011763:Pyrrolizidine Alkaloids / Q000737:chemistry; D013559:Symbiosis / Q000502:physiology
chemical_list: D000470:Alkaloids; D011763:Pyrrolizidine Alkaloids; C059478:loline