A discarded plastic bottle can supply building blocks for another chemical. Researchers at the University of Edinburgh combined chemical processing and engineered bacteria to make paracetamol, also called acetaminophen, from a PET-derived molecule. The result opens an intriguing manufacturing question: which parts of a waste material can biology help transform? [8]
The peer-reviewed study by Nick W. Johnson and colleagues was published online in Nature Chemistry on 23 June 2025. [1]
A bottle is a chain of smaller building blocks
PET stands for polyethylene terephthalate, a polyester used in packaging and textiles. Its repeated chemical units form long chains. Breaking those chains into smaller components is called depolymerization. Recovering building blocks creates an opportunity to make another product, but the method used to release them remains part of the manufacturing process. [2]
One separate line of research uses enzymes to cut PET. In 2020, Vincent Tournier and colleagues reported an engineered PET hydrolase and demonstrated recycling recovered material into new bottles. Their experiments also showed why plastic structure and enzyme stability matter: a material's crystallinity and the reaction conditions influence how accessible its chains are. [2]
That work provides useful context, rather than the method used for the featured paracetamol result. Enzymatic depolymerization, chemical preparation and microbial conversion answer different questions. Joining them into a useful process requires checking each connection.
How can a chemical reaction help a cell grow?
An auxotroph is an organism unable to make a nutrient it needs. If that nutrient is absent, growth can stop. This makes auxotrophy useful experimentally: a reaction that supplies the missing nutrient can produce a detectable biological response. The experiment links chemistry to a function the cell must perform. [3]
In 2013, Yunmi Lee, Afoma Umeano and Emily Balskus demonstrated this approach with nonenzymatic reactions and E. coli. Their work included generating PABA, a precursor needed for folate synthesis, to support nutrient-deficient strains. Appropriate controls compared complete reaction mixtures with conditions missing essential components. [3]
The reasoning is simple: a reaction must work in the biological setting and supply something usable. A substance that kills the cells, or produces the wrong compound, cannot provide the intended rescue. Growth is evidence about compatibility; chemical analysis establishes which molecules appeared.
A chemical step that can cooperate with metabolism
The reaction at the centre of this research is a Lossen rearrangement, which changes a prepared starting compound into an amine-containing product. Nick Johnson's 2024 doctoral thesis described making this chemistry compatible with living bacteria in water-based growth medium at 37 °C. It also described rescuing auxotrophic strains and linking reaction products to engineered biosynthesis. That thesis is earlier doctoral research, distinct from the later peer-reviewed article. [4]
Here, nonenzymatic means the chemical step does not depend on an enzyme catalysing that transformation. Biocompatible means it can operate alongside the biological system under the conditions tested. Neither term means that every reagent is suitable for every organism or use. The useful design idea is to give chemistry and metabolism complementary jobs. [4]
Bacterial paracetamol production had an earlier foundation
Scientists had already investigated microbial paracetamol synthesis before the plastic-derived route. In a 2021 Green Chemistry paper, Feifei Hou, Mo Xian and Wei Huang engineered E. coli to make paracetamol from glucose or glycerol. Their approach combined enzymes from different sources, protein engineering and changes intended to improve how material moved through the pathway. [5]
The study reported 942.5 mg per litre in a fed-batch 5-litre fermenter. It also examined whole-cell conversion using PABA as a starting material. These were different production arrangements with different inputs. The results established a biological route to the target molecule; they did not establish the later plastic-waste conversion. [5]
This history helps locate the new contribution. A microbial pathway can already exist while access to a different feedstock remains unsolved. Connecting a waste-derived input to that pathway can therefore be a meaningful research advance.
What the 2025 study actually did
Researchers chemically processed waste PET into terephthalic acid, then prepared the substrate called PET-1. A phosphate-catalysed Lossen reaction generated PABA. Engineered E. coli supplied enzymes for subsequent conversion through 4-aminophenol to paracetamol. The optimized procedure initiated the chemical step at 50 °C before adding cells for biotransformation at 37 °C. [1]
The paper reported 92% paracetamol yield from PET-1 under its optimized conditions. It used analytical measurements, including HPLC and NMR, and reported replicate experiments. This yield concerns the prepared substrate in the specified conversion. It is not an overall bottle-to-medicine mass yield. [1]
A useful way to read a yield is to ask what enters its denominator. Starting with a purified intermediate leaves earlier processing outside that particular comparison. Likewise, measuring a desired compound in a reaction mixture does not by itself show how efficiently it can be isolated at a required purity.
The product depends on the pathway
Related research illustrates the range of possible destinations for PET-derived material. A 2023 study by Marcos Valenzuela-Ortega and colleagues used engineered E. coli to produce adipic acid, an industrial chemical associated with nylon manufacture. The researchers optimized gene expression and enzyme activity, and immobilized cells in alginate hydrogels to improve the stability of a limiting enzyme. [6]
Their experiments included terephthalate recovered from industrial PET waste and a post-consumer bottle. This was a separate pathway and product. Together, the examples show why “plastic upcycling” describes a family of processes rather than a single biological ability. Choosing the target molecule changes the enzymes, operating conditions and separation problem. [6]
Environmental benefit needs a whole-process comparison
Using a waste feedstock is a promising starting point for sustainability, but the full process matters. A 2022 life-cycle assessment by Taylor Uekert and colleagues examined enzymatic PET recycling, including collection, processing, chemicals and electricity. For its modelled base case, several impacts exceeded those of virgin-material production; sensitivity analysis identified changes that could improve performance. [7]
That analysis did not assess this paracetamol route. Its relevance is methodological: environmental conclusions depend on the system boundary, background data and assumptions. A cool biological step can coexist with resource-intensive preparation or purification elsewhere. Climate claims therefore need a comparison that includes those stages, rather than being inferred from the presence of bacteria. [7]
What would turn the idea into a useful process?
The featured work is a laboratory proof of concept. The authors identify bioreactor development, product isolation and quantitative sustainability assessment as future priorities. It does not establish a commercial manufacturing process or a patient-ready medicine. [1]
A practical next evaluation would track the entire chain: the composition of incoming waste, recovery through preparation, consistent biological conversion and purification of the target product. It would compare costs and environmental effects using equivalent product quality and quantities. These are proposed evaluation questions, rather than additional results reported here.
The memorable idea is that a discarded material can become a chemical resource when researchers design the connections carefully. Chemistry prepares an input; biological machinery performs selected transformations. Demonstrating those connections is the beginning of a manufacturing story, with performance at scale still to be measured.
Sources and references
- Johnson NW et al. A biocompatible Lossen rearrangement in Escherichia coli. Nature Chemistry 17, 1020–1026 (2025). Published online 23 June 2025. Peer-reviewed research.
- Tournier V et al. An engineered PET depolymerase to break down and recycle plastic bottles. Nature 580, 216–219 (2020).
- Lee Y, Umeano A, Balskus EP. Rescuing Auxotrophic Microorganisms with Nonenzymatic Chemistry. Angewandte Chemie International Edition 52, 11800–11803 (2013).
- Johnson NW. Development of a biocompatible lossen rearrangement in Escherichia coli. University of Edinburgh doctoral thesis (2024). Repository issue date 18 October 2024; not a peer-reviewed journal article.
- Hou F, Xian M, Huang W. De novo biosynthesis and whole-cell catalytic production of paracetamol on a gram scale in Escherichia coli. Green Chemistry 23, 8280–8289 (2021).
- Valenzuela-Ortega M, Suitor JT, White MFM, Hinchcliffe T, Wallace S. Microbial Upcycling of Waste PET to Adipic Acid. ACS Central Science 9, 2057–2063 (2023).
- Uekert T et al. Life cycle assessment of enzymatic poly(ethylene terephthalate) recycling. Green Chemistry 24, 6531–6543 (2022).
- Edinburgh Innovations. Microbes transform plastic waste into paracetamol. Original research-institution news account, 23 June 2025. Used for general context; experimental conditions and yield follow the primary paper.
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