De novo biosynthesis of paracetamol from glucose by metabolically engineered Escherichia coli

Background: Paracetamol is among the most commonly used of all medications, widely accepted as a safe and effective analgesic/antipyretic for mild-to-moderate pain and fever. The biosynthesis of paracetamol from renewable sugars has not been reported so far, due to the lack of natural biosynthetic pathways. Results: In this study, we demonstrated for the first time the development of an E. coli cell factory for production of paracetamol from glucose. First, p-aminobenzoic acid, an intermediate of folic acid in microorganism, is selected as precursor substrates for the production of paracetamol. Second, a monooxygenase MNX1 from Candida parapsilosis CBS604 that can efficiently catalyze the decarboxylation and hydroxylation of p-aminobenzoic acid into corresponding p-aminophenol and another N-acetyltransferase PANAT from Pseudomonas aeruginosa that can efficiently catalyze the esterification of acetyl-CoA and p-aminophenol to form paracetamol were discovered. Finally, an engineered E. coli that allows production of paracetamol from simple carbon sources was established. Conclusions: The present study opens up a new direction for engineering microbial production of paracetamol from cheap and readily-available renewable raw materials such as sugars and cellulose in the future.