Imagine turning plastic bottle waste into life-saving medicine. This is the exciting prospect unveiled by scientists who have engineered Escherichia coli (E. coli) bacteria to perform just such a feat, converting components of recycled PET plastic into paracetamol (acetaminophen), a common painkiller.
This groundbreaking research, published in Nature Chemistry, represents a significant step towards creating more sustainable manufacturing processes for pharmaceuticals and finding innovative ways to manage the mounting global plastic waste crisis.
Merging Chemistry and Biology
For decades, synthetic organic chemistry and biological processes in living cells have largely existed as separate realms. Nature excels at complex, enzyme-driven reactions essential for life, while synthetic chemistry offers a vast array of transformations not seen in biology, often requiring conditions (like high temperatures, pressures, or harsh chemicals) that are incompatible with living cells.
The challenge for chemical biotechnology is to bridge this gap – to integrate non-biological chemistry into living systems. This would unlock new possibilities for producing valuable chemicals sustainably from renewable resources or waste.
A “New-to-Nature” Chemical Reaction in Living Cells
Researchers have now successfully introduced a specific chemical reaction, known as the Lossen rearrangement, into living E. coli bacteria. Discovered over 150 years ago, the Lossen rearrangement typically transforms activated carboxylate substrates into primary amines. While useful in the lab, it had never been demonstrated to work inside living cells or interfaced with their metabolism.
Getting this reaction to run safely and efficiently within a complex cellular environment like E. coli was the initial hurdle. The team designed a specific molecule – an activated acyl hydroxamate – that was intended to undergo the Lossen rearrangement.
The Surprising Role of Phosphate
To test if this reaction was biocompatible and could integrate with cellular processes, the scientists used a clever strategy: they fed the designed molecule to an E. coli strain that was unable to produce a vital nutrient called para-aminobenzoic acid (PABA). PABA is essential for bacterial growth. The designed molecule was intended to rearrange via the Lossen reaction to produce PABA. If the reaction worked inside the cells without harming them, the bacteria would start growing.
Remarkably, the E. coli grew, confirming the Lossen rearrangement was indeed biocompatible and generating PABA in situ. Even more surprisingly, initial tests showed the reaction happened even without adding special catalysts! Further investigation revealed the catalyst was already present: phosphate. Common phosphate ions (like HPO₄²⁻), abundant in standard growth media and inside cells, were found to effectively catalyze the Lossen rearrangement under mild, aqueous conditions compatible with life. This highlights a previously unrecognized role for phosphate in cellular chemistry.
Upcycling Plastic Waste: Fueling Bacteria with PET
With the Lossen rearrangement successfully working in E. coli, the team turned their attention to a significant real-world problem: plastic waste. Polyethylene terephthalate (PET), the plastic used in millions of bottles and packaging, is a major pollutant. It can be broken down into terephthalic acid.
The researchers discovered they could synthesize the Lossen rearrangement substrate – the molecule the E. coli needed – directly from terephthalic acid derived from discarded PET bottle flakes. They created a version of the substrate (dubbed PET-1) sourced entirely from plastic waste.
Feeding this PET-derived substrate to the PABA-deficient E. coli also resulted in healthy bacterial growth. This demonstrated a powerful concept: components from plastic waste could be converted via the phosphate-catalyzed Lossen rearrangement into a molecule essential for microbial life, effectively linking plastic upcycling to biological production. The bacteria were, in a sense, being fueled by plastic-derived material.
From Plastic to Paracetamol: A Sustainable Pathway
The ultimate goal was to use this plastic-fueled process to create a high-value product. Paracetamol production traditionally relies on fossil fuels and generates considerable emissions. Could the plastic-derived PABA be the starting point for a greener synthesis?
The scientists further engineered the E. coli by introducing two genes from other microorganisms – one from a fungus and one from soil bacteria. These genes provided the bacteria with new enzymatic capabilities: specific enzymes (an aminobenzoate hydroxylase ABH60 and an arylamine N-acyltransferase PANAT) that could convert the PABA produced by the Lossen reaction into 4-aminophenol, and then finally into paracetamol (para-hydroxyacetanilide).
By combining the phosphate-catalyzed Lossen rearrangement of the PET-derived substrate with these newly equipped bacteria, the researchers achieved impressive results. They developed a process where the PET-derived material was converted into paracetamol with high yields – reaching up to 92% efficiency from the purified plastic-derived substrate and around 83% when starting from actual plastic waste components. This was achieved under mild conditions (starting the Lossen reaction at 50°C, then adding bacteria at 37°C), without the harsh chemicals or high energy typically needed for synthetic paracetamol production. The entire conversion from the plastic-derived molecule to paracetamol could be completed in under 48 hours, producing no detectable toxic byproducts.
Future Implications
This research offers a glimpse into a future where biotechnology and synthetic chemistry work hand-in-hand to solve pressing environmental and industrial challenges. By successfully integrating a fundamental chemical reaction into living cells and linking it to plastic waste streams, the team has opened new avenues for bio-based manufacturing.
While currently a proof-of-concept, this work lays the foundation for potentially developing scalable, low-emission processes to transform plastic waste into valuable chemicals and pharmaceuticals. Future steps include optimizing the process for large-scale bioreactors, potentially integrating the initial plastic breakdown step, and conducting life cycle assessments to fully evaluate the environmental impact.
This breakthrough demonstrates the power of biological engineering combined with innovative chemistry to create sustainable solutions for a circular economy.
