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Natural Products


ties and pinpointing their metabolic functions is very difficult. Comprehensive


transcriptome


The first de novo assembly of a Panax genome – sequencing


allowed the Choi team to overcome this barrier. They were able to identify 76 cytochrome P450s and classify them into unique families, which should enable their individual functions to be pre- dicted with accuracy. They were also able to piece together another


crucial puzzle: antibiotic biosynthesis. This is actu- ally where they found the highest number of iso- forms (1,250) and enzymes (135). “From this data, it can be affirmed that a num-


ber of antibiotics can be obtained from this plant,” the authors wrote.


A case for ginseng Until recently, researchers had to rely on patchy genomic and transcriptomic data in their quest to get to the root of one of the oldest and most pop- ular traditional medicines of East Asia: ginseng. Purported to have therapeutic effects on neu-


rodegenerative disorders, cardiovascular diseases, diabetes and cancer, Panax ginseng and Panax notoginseng contain unique saponins called gin- senosides. Study into these glycosylated triterpenes has been hampered, however, due to the slow growth (~4 years/generation), long generation time, low seed production and complicated genome structure of Panax plants.


One of the oldest and most


popular traditional medicines of East Asia, ginseng is


purported to have therapeutic effects on neurodegenerative disorders, cardiovascular


diseases, diabetes and cancer.


Genetics studies of the ginseng plant has helped researchers identify how bioactive


gensenosides are produced. Photo by Damien Dempsey


a 2.36 Gbp diploid P. notoginseng with 35,451 protein-encoding genes – was finally reported as a pre-print in July 20185 by a team from the Chinese University of Macau led by Simon Ming-Yuen Lee. A de novo assembly of a 2.98 Gbp genome (with 59,352 annotated genes) of the tetraploid P. gin- seng cultivar Chunpoong (ChP), produced by a team from Seoul National University led by Tae Jin Yang, followed shortly thereafter6. Sequencing of both DNA and mRNA enabled


researchers to take deep dives into not only the gin- senoside biosynthetic machinery, but also its regu- lation and metabolic utilisation. In the case of P. ginseng, Yang et al constructed genome-scale metabolic networks covering nearly 5,000 gene products, catalysing 2,194 reactions and 2,003 unique metabolites. Ginsenosides accumulate differently in roots,


leaves, stems, flower buds and berries, in quantities varying with tissue, age, environment and cultivar. Yang’s team was able to determine from whole-


genome sequencing that the high ginsenoside con- tents in older P. ginseng roots are likely the result of transportation from shoot tissues rather than active biosynthesis. Co-expression analysis using RNA sequencing data identified important enzymes with which ginsenoside production co-evolved. In the case of P. notoginseng, two types of gin- senosides (PPD and PPT) with opposing biological


56


Drug Discovery World Spring 2019


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