How a new reaction in E. coli helps recycle plastic into paracetamol

How a new reaction in E. coli helps recycle plastic into paracetamol

Scientists are using a new reaction in E. coli to turn discarded plastics into life-saving medicines, setting up a sustainable route for chemical manufacturing.

AA comparison of strategies for C-N bond formation through loss rearrangements in synthetic organic chemistry or through chorismate pathways in cellular metabolism.bThe proposed fusion of non-enzymatic waste-loss chemistry with cellular metabolism for sustainable synthesis and bio-upcycling of plastic waste. LG, group leaves.

In a recent studypublished in the journalNatural chemistryThe researchers demonstrated a unique experiment in which they were activatedEscherichia coliBacteria catalyze a classic but novel chemical reaction:The catalytic transformation of activated acyl hydroxamates into amines.

Their experiment marks a breakthrough in the relatively nascent field of biocompatible reactions. It allowed researchers to use loss retransmission, a catalytic reaction of synthetic organic chemistry new in nature, to convert plastic (polyethylene terephthalate [PET]) waste into paracetamol. By mixing synthetic chemistry with living systems, the study is pioneering a new wave of bioperation in which microbes recycle our waste and give us life-saving medicines.

background

The global biotechnology machinery uses microbes, particularly Escherichia coli, as workhorses for the cheap, efficient, and large-scale production of several valuable chemicals. Unfortunately, traditional biotechnology is limited in its ability to manipulate the genetic toolkits of microbes and severely limits the scope of its applications. Several chemical reactions, such as loss-loss rearrangement, remain limited to synthetic chemistry laboratories and their associated scalability disadvantages.

To address this limitation and expand the impact of biotechnology, a relatively novel concept called “biocompatible chemistry” is rapidly gaining momentum. The concept combines human non-enzymatic organic reactions and natural cellular metabolism, which significantly expands the raw material microbes that can produce them.

While biocompatible chemistry could theoretically make it possible to convert genetically modified microbes to convert waste into biofuels or even pharmaceuticals, the complex challenge of achieving non-toxic, efficient chemistry under physiological conditions must be met. So far, achieving this delicate balance has remained a significant challenge.

About the study

In the present study, researchers found that phosphate ions present in standard bacterial growth media can catalyze loss rearrangement under biologically compatible conditions. Described in 1872 by Wilhelm Losssen, this previously synthetic chemistry laboratory-limited experiment involves the phosphate-catalyzed rearrangement of a phenylhydroxamate ester into a primary amine product.

To reproduce loss rearrangements in living cells, the researchers first synchronized an activated hydroxamate substrate with a para-carboxyl group. In aqueous M9 media at 37 °C, phosphate in the growth medium catalyzes this substrate into para-aminobenzoate (PABA), an essential precursor for folate biosynthesis.

They tested the setup using auxotrophic E. coli strains that lacked PABA/B (δPABB or ΔPABA/B) or AROC genes, so after the loss substrate was added, the bacteria resumed growth, a process called “auxotroph rescue.” This suggests that the bacteria can now perform the loss reaction and use this product as a nutrient source, serving as a clear functional readout that the reaction has successfully integrated into E. coli metabolism.

To demonstrate the application potential of this new E. coli strain, researchers conducted two sequential experiments: 1. PET-derived substrate and 2. Paracetamol synthesis. The researchers first processed a bottle of polyethylene terephthalate (PET) into a hydroxamate loss precursor outside the cell. They then grew a nutrient-targeted culture of their engineered E. coli on its loss precursor, recovering what was recovered (at a rate of approximately 0.33 H⁻¹), demonstrating the conversion of plastic to nutrient.

Finally, they used genetically modified E. coli strains expressing O₂- and NADH-dependent aminobenzoate hydroxylase (ABH60) and acetyl-CoA-dependent arylamine N-acyltransferase (PANAT) genes, sourced from a fungus and another bacterium, respectively, to convert their Lossen precursor into para-hydroxyacetanilide (paracetamol). Initial attempts with a single technical load resulted in the formation of undesirable side products; The researchers addressed this by developing a more efficient two-strain system, with each strain performing one step of conversion.

Study results

This study marks a milestone in biocompatible chemistry research, demonstrating that chemically synthesized non-enzymatic organic compounds can be integrated into the natural world and processed using pre-existing host metabolism, significantly expanding the scope of tomorrow's biotechnology. His results showed that loss rearrangement, a chemical reaction previously limited to specialized chemistry laboratories, was achievable under routine aqueous physiological conditions and in vivo.

The study identified auxotrophic E. coli strains capable of converting a tailored loss substrate into growth disorder (PABA), confirming the integration of loss rearrangement into the bacteria's cellular machinery.

The study further revealed that these engineered bacteria were able to convert not only PET waste (bioremediation), but also their genetically improved subvariants (ABH60 and Panat-expressing strains) into paracetamol.

Finally, the study confirmed that this system functioned similarly in a range of loss substrates and reaction targets, indicating a generalizable platform for non-native chemical transformations in living cells.

Conclusions

The present study shows the potential of biocompatible chemistry research in the revolutionized chemical production of tomorrow. It demonstrates a novel strain of E. coli bacteria that can combine human ingenuity with its natural cellular machinery to achieve loss rearrangement. It channels the resulting products into growth and pharmaceutical production, even from plastic waste (PET).

This research blurs the line between chemistry and biotechnology and offers a novel route to upcycle materials and synthesize value-added compounds. While this process is currently proof of principle and return on investment optimization and path setting, this work provides a foundation for sustainable, cell-based systems that fuse abiotic reactions with metabolism.

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