Paracetamol, a pain medication also known as acetaminophen, is traditionally made from dwindling supplies of fossil fuels including crude oil. Thousands of tons of fossil fuels are used annually to power the factories that produce the painkiller, alongside other medicines and chemicals. University of Edinburgh’s Professor Stephen Wallace and colleagues have found that Escherichia coli bacteria can convert a molecule derived from a waste plastic bottle into paracetamol.
Johnson et al. report a biocompatible Lossen rearrangement that is catalyzed by phosphate in the bacterium Escherichia coli for the transformation of activated acyl hydroxamates to primary amine-containing metabolites in living cells. Image credit: Johnson et al., doi: 10.1038/s41557-025-01845-5.
The plastic waste problem is an ever-growing issue, and developing sustainable ways to upcycle plastic remains a priority.
Metabolic engineering — harnessing the network of chemical reactions used in a biological cell to produce desirable molecules — can be combined with organic chemistry to create new small molecules.
However, whether these reactions can be combined to upcycle plastic into a useful product is unclear.
“Our work demonstrates that polyethylene terephthalate (PET) plastic isn’t just waste or a material destined to become more plastic — it can be transformed by microorganisms into valuable new products, including those with potential for treating disease,” Professor Wallace said.
In their research, Professor Wallace and co-authors found that a type of chemical reaction called a Lossen rearrangement can take place in living cells, catalyzed by phosphate from inside Escherichia coli (E. coli).
This chemical reaction produces a type of nitrogen-containing organic compound that is essential for cellular metabolism.
The researchers used chemical methods to degrade a PET plastic bottle to produce the starting molecule for the chemical reaction and show that cellular metabolism can then remediate this plastic-derived molecule.
They also found that this plastic-derived molecule can be used as a starting material for producing paracetamol in E. coli with a 92% yield.
The findings may present the first instance of paracetamol being produced from E. coli using a waste product.
Further research could involve studying how other types of bacteria or plastic may generate useful products.
“Biocompatible chemistry should therefore be considered as complementary to nascent work in enzyme design and engineering for abiotic chemistry and integrated cooperatively as a tool in living cells to expand the synthetic chemistry that is possible within engineered biological systems,” the scientists said.
The team’s work was published June 23, 2025 in the journal Nature Chemistry.
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N.W. Johnson et al. A biocompatible Lossen rearrangement in Escherichia coli. Nat. Chem, published online June 23, 2025; doi: 10.1038/s41557-025-01845-5
