Current Status and De Novo Synthesis of Anti-Tumor Alkaloids in Nicotiana: A Mini-Review

Abstract

Alkaloids are the most diversified nitrogen-containing secondary metabolites having antioxi-dant, and antimicrobial properties and are extensively used in pharmaceuticals to treat different types of cancer. Nicotiana serves as a reservoir of anticancer alkaloids and is also used as a model plant for the de novo synthesis of various anti-cancer molecules through genetic engineering. Up to 4% of the total dry weight of Nicotiana was found to be composed of alkaloids where nicotine, nornicotine, anatabine, and anabasine are reported as the dominant alkaloids. And, among the alkaloids present in Nicotiana, β-carboline (Harmane and Norharmane), Kynurenines are found to show anti-tumor effects, especially in the case of colon and breast cancer. Creating new or shunting of existing biosynthesis pathways in different species of Nicotiana resulted in de novo or increased synthesis of different anti-tumor molecules or their derivatives or precursors includ-ing Taxadiane (~22.5 µg/g), Artemisinin (~120 μg/g), Parthenolide (~2.05 ng/g), Costunolide (~60 ng/g), Etoposide (~1 mg/g), Crocin (~400 µg/g), Catharanthine (~60 ng/g), Tabersonine (~10 ng/g), Strictosidine (~0.23 mg/g), etc. Enrich precursor pool especially Dimethylallyl Diphos-phate (DMAPP) and down-regulating of other bi-product pathways, compartmentalization or metabolic shunting, or organelle-specific reconstitution of the precursor pool might trigger the enhanced accumulation of the targeted anticancer alkaloid in Nicotiana.