Biosynthesis of Lycopodine. The Question of the Intermediacy of Piperidine-2-acetic Acid

Marshall, William D.; Nguyen, Thanh Tra; MacLean, David B.; Spenser, Ian D.

doi:10.1139/v75-005

Cited by 30 publications

(13 citation statements)

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“…As no differences were observed in retention time and in fragmentation pattern (Figure ), it could be concluded that the samples actually contained the esters of homopipecolic acid and homoproline. Homopipecolic acid was described before in Lycopodium species as an intermediate of the synthesis of Lycopodium alkaloids, while homoproline was isolated from Asteraceae species, as a precursor of pyrrolizidines, but their co‐occurrence has never been reported in plants and their biosynthetic origin is not known.…”

Section: Resultsmentioning

confidence: 99%

“…Homopipecolic acid was described before in Lycopodium species as an intermediate of the synthesis of Lycopodium alkaloids, 41,42 while homoproline was isolated from Asteraceae species, as a precursor of pyrrolizidines, 40 but their co-occurrence has never been reported in plants and their biosynthetic origin is not known.…”

Section: Identification Of Beta Amino Acid Derivativesmentioning

confidence: 99%

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Phytochemical analysis of Ononis arvensis L. by liquid chromatography coupled with mass spectrometry

et al. 2019

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Ononis arvensis L. can be found overall in Europe and is used to treat infections of the urinary tract and skin diseases in ethnopharmacology. Flavonoids, hydroxycinnamic acids, oxycoumarin, scopoletin and scopolin, phytosterols, lectins, and some selected isoflavonoids were identified in O. arvensis till date; however, there is a lack of the detailed investigation of the isoflavonoid profile of the plant. With the application of high‐resolution tandem mass spectrometry, the fragmentation patterns of isoflavonoid derivatives found in O. arvensis roots and aerial parts were investigated and discussed. Isoflavonoid glucosides, glucoside malonates, aglycones, and beta amino acid derivatives were characterized, among which homoproline isoflavonoid glucoside esters were described for the first time. Besides the known isoflavonoid aglycones described earlier in other Ononis species, two 2′‐methoxy isoflavonoid derivatives were detected. The presence of licoagroside B was verified, and its structure was also corroborated by NMR experiments. Altogether, the high‐resolution fragmentation pattern of 47 isoflavonoids and glycosides is presented, and their relative quantity in the roots and the aerial parts can be evaluated. Based on this information, the chemotaxonomic relation of Ononis species and the biosynthesis of their compounds could be comprehended to a greater depth.

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Section: Resultsmentioning

confidence: 99%

Section: Identification Of Beta Amino Acid Derivativesmentioning

confidence: 99%

Phytochemical analysis of Ononis arvensis L. by liquid chromatography coupled with mass spectrometry

et al. 2019

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“…Through previous isotope labeling studies, 28,29 the Lycopodium alkaloids have been shown to be derived from L-lysine and malonyl-CoA (Figure 2a). Although biosynthetic hypotheses have been developed based upon these studies in addition to several others, 23 the underlying enzymes for the majority of Lycopodium alkaloid biosynthesis have not yet been elucidated.…”

Section: Case Study 1: Timing and Tissue Specificity Of Huperzine A Bmentioning

confidence: 99%

D₂O Labeling to measure active biosynthesis of natural products in medicinal plants

et al. 2018

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Plant natural products have served as a prominent source of medicines throughout human history, and are still used today as clinically-approved pharmaceuticals. However, many medicinal plants that produce useful compounds are slow-growing or recalcitrant to cultivation, making it difficult to investigate the underlying genetic/enzymatic machinery responsible for biosynthesis. To better understand the metabolism of bioactive natural products in slow-growing medicinal plants, we used D2O labeling and LC-MS-based metabolomics to explore the biosynthesis of medically-relevant alkaloids in three plant species. Our results provide evidence for sites of active biosynthesis for these alkaloids, and demonstrate that D2O labeling can be used as a general method to determine sites of active secondary metabolism over relatively short time scales. We anticipate that these results will facilitate discovery of complete metabolic pathways for plant natural products of medicinal importance, especially for approaches that rely upon transcriptomics and knowledge of active metabolism to identify biosynthetic enzymes.

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“…Several recent studies identified a type III polyketide synthase (PKS) and its corresponding gene in H. serrata [ 13 , 14 ]. A proposed biosynthesis pathway for the synthesis of Hup A and related lycopodium alkaloids consisting of pelletierine coupled with 4PAA was reported by Ma and Gang (2004) [ 4 ] based on previous studies [ 15 - 18 ]. Initially, L-lysine is decarboxylated by lysine decarboxylase to form cadaverine.…”

Section: Introductionmentioning

confidence: 99%

Comparison of 454-ESTs from Huperzia serrata and Phlegmariurus carinatus reveals putative genes involved in lycopodium alkaloid biosynthesis and developmental regulation

et al. 2010

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BackgroundPlants of the Huperziaceae family, which comprise the two genera Huperzia and Phlegmariurus, produce various types of lycopodium alkaloids that are used to treat a number of human ailments, such as contusions, swellings and strains. Huperzine A, which belongs to the lycodine type of lycopodium alkaloids, has been used as an anti-Alzheimer's disease drug candidate. Despite their medical importance, little genomic or transcriptomic data are available for the members of this family. We used massive parallel pyrosequencing on the Roche 454-GS FLX Titanium platform to generate a substantial EST dataset for Huperzia serrata (H. serrata) and Phlegmariurus carinatus (P. carinatus) as representative members of the Huperzia and Phlegmariurus genera, respectively. H. serrata and P. carinatus are important plants for research on the biosynthesis of lycopodium alkaloids. We focused on gene discovery in the areas of bioactive compound biosynthesis and transcriptional regulation as well as genetic marker detection in these species.ResultsFor H. serrata, 36,763 unique putative transcripts were generated from 140,930 reads totaling over 57,028,559 base pairs; for P. carinatus, 31,812 unique putative transcripts were generated from 79,920 reads totaling over 30,498,684 base pairs. Using BLASTX searches of public databases, 16,274 (44.3%) unique putative transcripts from H. serrata and 14,070 (44.2%) from P. carinatus were assigned to at least one protein. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology annotations revealed that the functions of the unique putative transcripts from these two species cover a similarly broad set of molecular functions, biological processes and biochemical pathways.In particular, a total of 20 H. serrata candidate cytochrome P450 genes, which are more abundant in leaves than in roots and might be involved in lycopodium alkaloid biosynthesis, were found based on the comparison of H. serrata and P. carinatus 454-ESTs and real-time PCR analysis. Four unique putative CYP450 transcripts (Hs01891, Hs04010, Hs13557 and Hs00093) which are the most likely to be involved in the biosynthesis of lycopodium alkaloids were selected based on a phylogenetic analysis. Approximately 115 H. serrata and 98 P. carinatus unique putative transcripts associated with the biosynthesis of triterpenoids, alkaloids and flavones/flavonoids were located in the 454-EST datasets. Transcripts related to phytohormone biosynthesis and signal transduction as well as transcription factors were also obtained. In addition, we discovered 2,729 and 1,573 potential SSR-motif microsatellite loci in the H. serrata and P. carinatus 454-ESTs, respectively.ConclusionsThe 454-EST resource allowed for the first large-scale acquisition of ESTs from H. serrata and P. carinatus, which are representative members of the Huperziaceae family. We discovered many genes likely to be involved in the biosynthesis of bioactive compounds and transcriptional regulation as well as a large number of potential microsatellite m...

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Biosynthesis of Lycopodine. The Question of the Intermediacy of Piperidine-2-acetic Acid

Abstract: . 53, 41 (1375).In Lycopodirtm tristachyum lycopodine is derived from L-lysine whereas pipecolic acid is derived from D-lysine. Malonic acid serves as a specific precurser of the non-lysine derived segments of lycopodine. Pipendine-2-acetic acid is not incorporated into the alkaloid.

Cited by 30 publications

References 10 publications

Phytochemical analysis of Ononis arvensis L. by liquid chromatography coupled with mass spectrometry

Phytochemical analysis of Ononis arvensis L. by liquid chromatography coupled with mass spectrometry

D₂O Labeling to measure active biosynthesis of natural products in medicinal plants

Comparison of 454-ESTs from Huperzia serrata and Phlegmariurus carinatus reveals putative genes involved in lycopodium alkaloid biosynthesis and developmental regulation

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Biosynthesis of Lycopodine. The Question of the Intermediacy of Piperidine-2-acetic Acid

Abstract: . 53, 41 (1375).In Lycopodirtm tristachyum lycopodine is derived from L-lysine whereas pipecolic acid is derived from D-lysine. Malonic acid serves as a specific precurser of the non-lysine derived segments of lycopodine. Pipendine-2-acetic acid is not incorporated into the alkaloid.

Cited by 30 publications

References 10 publications

Phytochemical analysis of Ononis arvensis L. by liquid chromatography coupled with mass spectrometry

Phytochemical analysis of Ononis arvensis L. by liquid chromatography coupled with mass spectrometry

D2O Labeling to measure active biosynthesis of natural products in medicinal plants

Comparison of 454-ESTs from Huperzia serrata and Phlegmariurus carinatus reveals putative genes involved in lycopodium alkaloid biosynthesis and developmental regulation

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D₂O Labeling to measure active biosynthesis of natural products in medicinal plants