Ethyl Methane Sulfonate and Sodium Azide-Mediated Chemical and X-ray-Mediated Physical Mutagenesis Positively Regulate Gene Activity and Biosynthesis of Antineoplastic Vinblastine in .

synthesizes bioactive therapeutic metabolites, known as monoterpenoid indole alkaloids (MIAs), including antineoplastic vinblastine and vincristine, which have high global demand, and antihypertensive ajmalicine, a serpentine. However, the in planta biosynthesis and accumulation of these phytopharmaceuticals are very low, attributed to their high cytotoxicity in the plant. Considering the low in planta concentration and over-harvesting of plant resources, biotechnological interventions have been undertaken to enhance the production of MIAs in plant systems. The present study was carried out to mutation through chemical and physical mutagenesis with sodium azide, ethyl methane sulfonate and X-rays, respectively, on to determine their possible effects on the transcriptional modulation of MIA biosynthetic pathways in planta. The chemical mutagenesis resulted in delayed seed pod development in mutated plants, with distinct leaf morphology and flower color. However, X-ray mutagenesis resulted in pollen-less sterile flowers. An HPLC analysis confirmed the higher catharanthine, vindoline and vinblastine content in sodium azide and X-ray mutants, and was further supported by higher transcript levels estimated through real-time PCR analysis. The transcription factors and were found negatively regulated along with major MIA pathway genes in chemical mutants and their M generation, but showed positive regulation in X-ray M mutants. The induced mutagenesis of provides a prospective strategy to modulate plant transcriptomes and enhance the biosynthesis of pharmaceutically important antineoplastic vinblastine in the plant.