Nicotine biosynthesis is completed by cryptic activating glucosylation (opens in new tab)

Nicotine is a neuroactive alkaloid produced by tobacco (Nicotiana tabacum) as a defence against herbivory, and an addictive stimulant that has been used by humans for millennia. Despite its significance, the core steps of its biosynthesis have remained elusive. Here, we demonstrate the in vitro reconstruction of a four-enzyme stereoselective biocatalytic cascade that forms (S)-nicotine from nicotinic acid and N-methylpyrrolinium. This cascade includes two glucose-processing enzymes that parti...