Defining the rules of biocompatible chemistry

Biocompatible chemistry – the use of non-enzymatic, chemocatalytic reactions to interface with and manipulate cellular metabolism – has emerged as a powerful hybrid approach at the interface of synthetic chemistry and engineering biology. Early studies showed that abiotic catalysts can function in the presence of living cells and influence biological processes. More recent work demonstrates that such reactions can be integrated with native and engineered metabolism to access new chemical space, valorise waste feedstocks, and, in some cases, outperform conventional petrochemical processes from an environmental perspective. As the field matures, attention is shifting from proof-of-concept demonstrations to fundamental questions of mechanism: why some reactions are biocompatible, whether compatibility can be predicted or engineered, and where its limits lie. Addressing these questions, alongside defining practical boundaries, will be essential to realising the full potential of biocompatible chemistry in chemical biology, biotechnology, and sustainable manufacturing.