scholarly journals Systematic silencing of benzylisoquinoline alkaloid biosynthetic genes reveals the major route to papaverine in opium poppy

2012 ◽  
Vol 72 (2) ◽  
pp. 331-344 ◽  
Author(s):  
Isabel Desgagné-Penix ◽  
Peter J. Facchini
Science ◽  
2018 ◽  
Vol 362 (6412) ◽  
pp. 343-347 ◽  
Author(s):  
Li Guo ◽  
Thilo Winzer ◽  
Xiaofei Yang ◽  
Yi Li ◽  
Zemin Ning ◽  
...  

Morphinan-based painkillers are derived from opium poppy (Papaver somniferumL.). We report a draft of the opium poppy genome, with 2.72 gigabases assembled into 11 chromosomes with contig N50 and scaffold N50 of 1.77 and 204 megabases, respectively. Synteny analysis suggests a whole-genome duplication at ~7.8 million years ago and ancient segmental or whole-genome duplication(s) that occurred before the Papaveraceae-Ranunculaceae divergence 110 million years ago. Syntenic blocks representative of phthalideisoquinoline and morphinan components of a benzylisoquinoline alkaloid cluster of 15 genes provide insight into how this cluster evolved. Paralog analysis identified P450 and oxidoreductase genes that combined to form theSTORRgene fusion essential for morphinan biosynthesis in opium poppy. Thus, gene duplication, rearrangement, and fusion events have led to evolution of specialized metabolic products in opium poppy.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Dingqiao Xu ◽  
Hanfeng Lin ◽  
Yuping Tang ◽  
Lu Huang ◽  
Jian Xu ◽  
...  

AbstractCorydalis yanhusuo W.T. Wang is a classic herb that is frequently used in traditional Chinese medicine and is efficacious in promoting blood circulation, enhancing energy, and relieving pain. Benzylisoquinoline alkaloids (BIAs) are the main bioactive ingredients in Corydalis yanhusuo. However, few studies have investigated the BIA biosynthetic pathway in C. yanhusuo, and the biosynthetic pathway of species-specific chemicals such as tetrahydropalmatine remains unclear. We performed full-length transcriptomic and metabolomic analyses to identify candidate genes that might be involved in BIA biosynthesis and identified a total of 101 full-length transcripts and 19 metabolites involved in the BIA biosynthetic pathway. Moreover, the contents of 19 representative BIAs in C. yanhusuo were quantified by classical targeted metabolomic approaches. Their accumulation in the tuber was consistent with the expression patterns of identified BIA biosynthetic genes in tubers and leaves, which reinforces the validity and reliability of the analyses. Full-length genes with similar expression or enrichment patterns were identified, and a complete BIA biosynthesis pathway in C. yanhusuo was constructed according to these findings. Phylogenetic analysis revealed a total of ten enzymes that may possess columbamine-O-methyltransferase activity, which is the final step for tetrahydropalmatine synthesis. Our results span the whole BIA biosynthetic pathway in C. yanhusuo. Our full-length transcriptomic data will enable further molecular cloning of enzymes and activity validation studies.


2021 ◽  
Author(s):  
Theresa Catania ◽  
Yi Li ◽  
Thilo Winzer ◽  
David Harvey ◽  
Fergus Meade ◽  
...  

The STORR gene fusion event is considered a key step in the evolution of benzylisoquinoline alkaloid (BIA) metabolism in opium poppy as the resulting bi-modular protein performs the isomerization of (S)- to (R)- reticuline which is required for morphinan biosynthesis. Our previous analysis of the opium poppy genome suggested the STORR gene fusion event occurred before a whole genome duplication event 7.2 million years ago. Here we use a combination of phylogenetic, transcriptomic, metabolomic, biochemical and genomic analysis to investigate the origin of the STORR gene fusion across the Papaveraceae family. The pro-morphinan/morphinan subclass of BIAs was present in a subset of 10 Papaver species including P. somniferum (opium poppy) and this correlated with the presence of the STORR gene fusion with one important exception. P. californicum does not produce morphinans but it does contain a STORR gene fusion that epimerizes (S)- to (R)- reticuline when heterologously expressed in yeast. The high similarity of the amino acid sequence linking the two modules of STORR along with phylogenetic gene tree analysis strongly suggests the gene fusion occurred only once and between 17-25 million years ago before the separation of P. californicum from the other Papaver species. We discovered that the most abundant BIA in P. californicum is (R)- glaucine, a member of the aporphine subclass of BIAs. Only the (S) isomer of this compound has previously been reported from nature. These results lead us to conclude that the function of the STORR gene fusion is not exclusive to morphinan production in the Papaveraceae.


2019 ◽  
Vol 18 (6) ◽  
pp. 1457-1482 ◽  
Author(s):  
Aparna Singh ◽  
Ivette M. Menéndez-Perdomo ◽  
Peter J. Facchini

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