A biocompatible Lossen rearrangement in Escherichia coli

Nature has evolved an exquisite yet limited set of chemical reactions that underpin the function of all living organisms. By contrast, the field of synthetic organic chemistry can access reactivity not observed in nature, and integration of these abiotic reactions within living systems offers an elegant solution to the sustainable synthesis of many industrial chemicals from renewable feedstocks. Here we report a biocompatible Lossen rearrangement that is catalysed by phosphate in the bacterium Escherichia coli for the transformation of activated acyl hydroxamates to primary amine-containing metabolites in living cells. Through auxotroph rescue, we demonstrate how this new-to-nature reaction can be used to control microbial growth and chemistry by generating the essential metabolite para-aminobenzoic acid. The Lossen rearrangement substrate can also be synthesized from polyethylene terephthalate and applied to whole-cell biocatalytic reactions and fermentations generating industrial small molecules (including the drug paracetamol), paving the way for a general strategy to bioremediate and upcycle plastic waste in native and engineered biological systems. (Figure presented.)