Herbal genomics as tools for dissecting new metabolic pathways of unexplored medicinal plants and drug discovery

Abstract

Herbal drugs, on which 80% of the world's population rely, are relatively safe over conventional drugs. Conventional drugs are costly, have serious side effects and hence over the past few decades researchers have focused on drug discovery from herbal medicines or botanical sources. The majority of new herbal drugs have been generated from secondary metabolites (alkaloids, terpenoids and phenolic compounds) of plant metabolism. Till date, only a small fraction of the vast diversity of plant metabolism has been explored for the production of new medicines and other products. The emergence of new herbal genomics research, medicinal plant genomics consortium, together with advances in other omics information may help for the speedy discovery of previously unknown metabolic pathways and enzymes. This review highlights the importance of genomics research in the discovery of some previously unknown enzymes/pathways which may make significant contributions in plant metabolic biology and may be used for the future discovery of many new pharmaceutical agents.

Keywords: Drug; Genomics; Herbal; Metabolite.

Fig. 1

Biosynthetic pathway of podophyllotoxin in P. hexandrum. Chemical conversion of anticancer etoposide from podophyllotoxin is also shown. Uncharacterized steps in the pathway are indicated by dashed lines. DIR: dirigent protein, PLR: pinoresinol lariciresinol reductase, SDH: secoisolariciresinol dehydrogenase CYP: cytochrome P 450.

Fig. 2

Showing Olivetolic Acid Cyclase in the biosynthesis of cannabinoids, a unique biosynthetic route to plant polyketides. The enzyme cyclase catalyzes the formation of OA from hexanoyl CoA plus malonyl CoA (A). OA then converted to cannabigerolic acid and then to major cannabinoids, CBDA through enzymatic conversions. Finally, CBDA upon decarboxylation produces their neutral form CBD, cannabidiol.

Fig. 3

Iridoid synthase from C. roseus in alternate biochemical mechanism of iridoid biosynthesis. a) The synthase uses monoterpene 10 oxogeranial as substrate and NAD(P)H reduction step for cyclization, whereas b) monoterpene cyclases uses geranyl diphosphate as substrate in the usual process of cyclization.

Fig. 4

Valuable secondary metabolites produced by pathway engineering in plants. Chlorinated monoterpenoid indole alkaloids are generated from transformed hairy roots of Catharanthus.

Fig. 5

Some important structures from medicinal plants and the names of plants that produce them.