A new benzylisoquinoline alkaloid from stems of Nelumbo nucifera

A new benzylisoquinoline alkaloid, named nelumstemine （1）, 1-（4＇-hydroxybenzoyl）-6,7-dimethoxy-3,4-dihydroisoquinoline, was isolated from the stems of Nelumbo nucifera Geartn. Its structure was established on the basis of spectral analysis.

A New Benzylisoquinoline Alkaloid from Sabia parviflora

A new benzylisoquinoline alkaloid, 1, 2, 3, 4-tetrahydro-5-hydroxyl-8-methoxyl-2- methyl-4'-methoxyl-benzylisoquinoline, was isolated from the arial parts of Sabia parviflora. Its structure was established on the basis of spectral analysis.

The Genome of Medicinal Plant Macleaya cordata Provides New Insights into Benzylisoquinoline Alkaloids Metabolism

The overuse of antibiotics in animal agriculture and medicine has caused a series of potential threats to public health. Macleaya cordata is a medicinal plant species from the Papaveraceae family, providing a safe resource for the manufacture of antimicrobial feed additive for livestock. The active constituents from M. cordata are known to include benzylisoquinoline alkaloids （BIAs） such as sanguinarine （SAN） and chelerythrine （CHE）, but their metabolic pathways have yet to be studied in this non-model plant. The active biosynthesis of SAN and CHE in M. cordata was first examined and confirmed by feeding ^13C-labeled tyrosine. To gain further insights, we de novo sequenced the whole genome of M. cordata, the first to be sequenced from the Papaveraceae family. The M. cordata genome covering 378 Mb encodes 22,328 predicted protein-coding genes with 43.5% being transposable elements. As a member of basal eudicot, M. cordata genome lacks the paleohexaploidy event that occurred in almost all eudicots. From the genomics data, a complete set of 16 metabolic genes for SAN and CHE biosynthesis was retrieved, and 14 of their biochemical activities were validated. These genomics and metabolic data show the conserved BIA metabolic pathways in M. cordata and provide the knowledge foundation for future productions of SAN and CHE by crop improvement or microbial pathway reconstruction.

Engineering Saccharomyces cerevisiae to produce plant benzylisoquinoline alkaloids

Benzylisoquinoline alkaloids(BIAs)are a diverse family of plant natural products with extensive pharmacological properties,but the yield of BIAs from plant is limited.The understanding of BIA biosynthetic mechanism in plant and the development of synthetic biology enable the possibility to produce BIAs through microbial fermentation,as an alternative to agriculture-based supply chains.In this review,we discussed the engineering strategies to synthesize BIAs in Saccharomyces cerevisiae(yeast)and improve BIA production level,including heterologous pathway reconstruction,enzyme engi neering,expression regulation,host engineering and fermentation engineering.We also highlight recent meta bolic engineering advances in the production of BIAs in yeast.

UPLC-QTOF-MS FOR METABOLITES IDENTIFICATION IN CACO-2 CELLS OF BENZYLISOQUINOLINE ALKALOIDS IN NELUMBINIS PLUMULA

The aim of the study was to identify main metabolites of benzylisoquinoline alkaloids from Nelumbinis Plumula after biotransformation by Caco-2 cells.Caco-2 cells were seeded to a 6-well plate and cultured for a period of time until 80%of each well was filled with cells.Then,cell medium was replaced and the norcoclaurine,liensinine,isoliensinine and neferine were respectively added to

Synthesis and evaluation of benzylisoquinoline derivatives for their inhibition on pancreatic lipase and preadipocyte proliferation

The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, and the products were obtained by reductions. All these compounds were identified by MS, 1H NMR and 13 C NMR. The inhibitory activities on pancreatic lipase and preadipocyte proliferation for the synthesized compounds and alkaloids from Nulembo nucifera were assessed in vitro. Most of the compounds showed inhibitory activities on both pancreatic lipase and preadipocyte proliferation. Particularly, compounds 7p-7u and 9d-9f exhibited significant inhibitory activity on pancreatic lipase while compounds 7c, 7d, 7f, 7g, 7i, and 7j potently inhibited the proliferation of 3T3-L1 preadipocytes. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for human diseases.

Over 100 Million Years of Enzyme Evolution Underpinning the Production of Morphine in the Papaveraceae Family of Flowering Plants

Phylogenomic analysis of whole genome sequences of five benzylisoquinoline alkaloid(BIA)-producing species from the Ranunculales and Proteales orders of flowering plants revealed the sequence and timing of evolutionary events leading to the diversification of these compounds.(S)-Reticuline is a pivotal intermediate in the synthesis of many BIAs and our analyses revealed parallel evolution between the two orders,which diverged122 million years ago(MYA).Berberine is present in species across the entire Ranunculales,and we found co-evolution of genes essential for production of the protoberberine class.The benzophenanthridine class,which includes the antimicrobial compound sanguinarine,is specific to the Papaveraceae family of Ranunculales,and biosynthetic genes emerged after the split with the Ranunculaceae family110 MYA but before the split of the three Papaveraceae species used in this study at77 MYA.The phthalideisoquinoline noscapine and morphinan class of BIAs are exclusive to the opium poppy lineage.Ks estimation of paralogous pairs indicates that morphine biosynthesis evolved more recently than 18 MYA in the Papaver genus.In the preceding 100 million years gene duplication,neofunctionalization and recruitment of additional enzyme classes,combined with gene clustering,gene fusion,and gene amplification,resulted in emergence of medicinally valuable BIAs including morphine and noscapine.