Natural Products


A modern approach


to herbal healing mining plant genomes


Plants are stationary soldiers. Rooted to one spot, they are not able to chase nutrients or flee from herbivores and pathogens. So in addition to the basic metabolites they synthesise for their survival, they produce a diverse array of organic compounds through specialised biochemical pathways to counterattack threats. Some of these compounds have been found to combat human threats as well, and herbalists have been scouring these palettes of secondary metabolites for their health-promoting properties for centuries.


By Michelle Vierra


M


odern medicine also incorporates plant compounds. Around 80% of the world’s population already relies on


ethnobotanical remedies and plant drugs, such as the antineoplastic Taxol,


the antimalarial


artemisinin, the analgesic codeine, the antidiabetic allicin, and the cardiac depressant quinidine. The high cost of new drugs, unpalatable side-effects and microbial resistance are driving a constant and renewed public interest on alternative and comple- mentary medicine. Yet only a small fraction of the vast diversity of


plant metabolism has been explored. This is quickly changing, as synthetic biologists


set out to mine the quarry of alkaloids, terpenoids and phenolic plant compounds in order to manu- facture new natural products and molecular ‘pharmers’ try to identify ways to use the plants themselves as biopharmaceutical factories. The increased affordability and sophistication of genetic sequencing technology is making all of this


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possible. But is it being used to its full potential? How can the technology be best utilised in drug discovery and development? It is no longer enough to simply sequence bits of


a genome. In order to understand the full metabol- ic potential of plants, comprehensive genomic information must be combined with transcriptom- ic, proteomic and metabolomic data. We need to be able to answer questions such as: How are the genes coded? Where are they clustered? Clustered genes in Arabidopsis, for example, are enriched in phenylpropanoid and terpenoid metabolism. Gene duplication, such as whole-genome duplications (WGDs) and local (tandem) duplication (LDs), can also play an important role in specialised metabolism, including the expression of flavonoid related genes. Fortunately, sequencing technology has evolved


to equip researchers with the tools to tackle nearly all of these questions. Single Molecule, Real-Time (SMRT) Sequencing,


Drug Discovery World Spring 2019


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