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Ether bridge formation in loline alkaloid biosynthesis.

ABSTRACT: Lolines are potent insecticidal agents produced by endophytic fungi of cool-season grasses. These alkaloids are composed of a pyrrolizidine ring system and an uncommon ether bridge linking carbons 2 and 7. Previous results indicated that 1-aminopyrrolizidine was a pathway intermediate. We used RNA interference to knock down expression of lolO, resulting in the accumulation of an alkaloid identified as exo-1-acetamidopyrrolizidine based on high-resolution MS and NMR. Genomes of endophytes differing in alkaloid profiles were sequenced, revealing that those with mutated lolO accumulated exo-1-acetamidopyrrolizidine but no lolines. Heterologous expression of wild-type lolO complemented a lolO mutant, resulting in the production of N-acetylnorloline. These results indicated that the non-heme iron oxygenase, LolO, is required for ether bridge formation, probably through oxidation of exo-1-acetamidopyrrolizidine.

SUBMITTER: Pan J

PROVIDER: S-EPMC3929955 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Ether bridge formation in loline alkaloid biosynthesis.

Pan Juan J Bhardwaj Minakshi M Faulkner Jerome R JR Nagabhyru Padmaja P Charlton Nikki D ND Higashi Richard M RM Miller Anne-Frances AF Young Carolyn A CA Grossman Robert B RB Schardl Christopher L CL

Phytochemistry 20131226

Lolines are potent insecticidal agents produced by endophytic fungi of cool-season grasses. These alkaloids are composed of a pyrrolizidine ring system and an uncommon ether bridge linking carbons 2 and 7. Previous results indicated that 1-aminopyrrolizidine was a pathway intermediate. We used RNA interference to knock down expression of lolO, resulting in the accumulation of an alkaloid identified as exo-1-acetamidopyrrolizidine based on high-resolution MS and NMR. Genomes of endophytes differi ...[more]

PMID: 24374065

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