Researchers turn plastic into paracetamol

Researchers at the University of Edinburgh have engineered a strain of Escherichia coli that relies on small molecules from waste polyethylene terephthalate (PET) plastic bottles to survive. The synthetic metabolic process they designed converts nearly 100% of PET-derived substrates into the world’s most commonly used painkiller, acetaminophen, also called paracetamol in many parts of the world, including Scotland (Nature Chemistry 2025, DOI: 10.1038/s41557-025-01845-5).

Conventional pharmaceutical manufacturing has an enormous carbon footprint—55% more emission intensive than that of the automotive industry—but this new method leaves virtually no carbon emissions. The researchers say plastic waste could shift from being an environmental burden to a feedstock for pharmaceutical products.

Stephen Wallace, a chemical biotechnology researcher, led the work. The team is the first to combine the Lossen rearrangement—a synthetic reaction—with a living organism’s metabolic systems, and they did so without harming the cells or disrupting their natural biological functions.

Discovered in 1872 by Wilhelm Lossen, this nonenzymatic reaction converts hydroxamate esters into isocyanates and then amines. The researchers designed a rearrangement that starts from an O-acyl-substituted hydroxamate ester substrate and produces p-aminobenzoic acid (PABA), a nutrient essential for E. coli growth. When the team grew PABA-deficient E. coli cultures in the presence of the substrate and various transition-metal catalysts, they found that the bacteria grew even without catalysts being present. Further tests showed the Lossen substrate could be converted to PABA in the presence of phosphate in the growth medium.

“This reaction happens without enzymes, is well tolerated by cells, and is stimulated by phosphate and active bacterial metabolism—making it a promising route for biocompatible chemical transformations,” Wallace says.

Although the researchers initially wanted to see if synthetic products could be made safely in microbial cells, they realized that Lossen substrates could also be made from waste materials. Specifically, breaking down PET plastic to terephthalic acid can form a modified version of the Lossen substrate, called PET-1, which serves as a precursor for PABA production.

With this in mind, the team investigated if engineered E. coli could forge an entirely new metabolic pathway to produce acetaminophen from PET-1.

The resulting Lossen rearrangement begins at 50 °C in a phosphate buffer, followed by the addition of PABA-deficient E. coli cells, which express PANAT and ABH60—two microbial enzymes responsible for synthesizing paracetamol from PABA. Incubating the cells at 37 °C resulted in paracetamol production with an 83% yield from PET-1. Further optimization by adjusting the protein expression conditions resulted in an even higher yield of 92%.

Mikael Elias, a University of Minnesota biochemist not involved in the study, finds the 92% yield really impressive, saying augmenting biological systems with synthetic catalysts, cofactors, and incorporated unnatural amino acids could create a versatile platform, expanding the chemistry possible within these systems.

There is growing industry momentum toward sustainable manufacturing, but Elias says that implementing this technology commercially could face several barriers, including navigating complicated regulatory processes. That said, “The technology could integrate with existing enzymatic PET depolymerization technologies to create comprehensive and circular waste-to-pharmaceutical platforms,” he says.