From pollutant-protein engagement to programmable bioremediation: chemoproteomics as a design framework for emerging...

Emerging contaminant biodegradation is still interpreted mainly through pathway reconstruction, parent-compound removal, and metabolite identification. These approaches document biotransformation outcomes, but often fail to explain how degradation is initiated and routed at the protein level. Here, we reviewed probe-based, label-free, and structural chemoproteomic strategies, which can identify direct contaminant-binding proteins including transporters and membrane-associated systems. We argue that chemoproteomics should be viewed not as another omics layer, but as a mechanism-discovery platform for environmental biocatalysis. We propose a protein-centric framework that defines biodegradation as a pollutant fate-determination chain. In this model, pollutant-protein engagement and stress responses jointly determine whether a chemical is accumulated or converted into more hazardous products. This framework moves the field beyond pathway-centric description toward a predictive understanding of the endogenous protein networks. Such approaches will help to govern contaminant fate and can be harnessed for programmable bioremediation.