Advances in regulatory mechanism(s) and biotechnological approaches to modulate nicotine content in tobacco

More than 8 million deaths are caused by tobacco-related diseases every year. A staggering 1.2 million of those fatalities occur due to second-hand smoke exposure among non-smokers, but more than 7 million are due to direct tobacco use among smokers. Nicotine acts as the key ingredient triggering the addiction. The United States Food and Drug Administration (FDA) has classified more than 90 chemical components of tobacco and related smoke as hazardous or potentially hazardous leading to cancer, cardiovascular, respiratory, and reproductive disorders. Hence, reducing nicotine content has been the foremost objective to reduce health and death risks. Therefore, various biotechnological approaches for developing tobacco varieties with low nicotine concentrations are urgently required for the welfare of humankind. In recent years, numerous advancements have been made in nicotine-based tobacco research, suggesting regulatory components involved in nicotine biosynthesis and developing nicotine-less tobacco varieties through biotechnological approaches. This review highlights the various regulatory components and major approaches used to modulate nicotine content in tobacco cultivars.