Exozymes for Biomanufacturing: Toward Clarity and Precision in the Cell-Free Space

In biotechnology, the term ‘cell-free’ describes a wide range of established and emerging processes and technologies. However, broad application of the term ‘cell-free’ leads to confusion and ambiguity in the field, especially when applied to biomanufacturing. When engaging with investors, government agencies, and industry partners, we have found that the association of ‘cell-free’ with numerous technologies spanning diverse applications creates unnecessary confusion. As a result, we believe the lack of clarity complicates communication, impacts technology adoption, and creates challenges in securing funding and regulatory recognition. Specifically, in this opinion, we focus on terminology used to describe enzyme-driven biocatalytic approaches for manufacturing small molecules, often referred to as ‘cell-free biomanufacturing.’ This ‘cell-free’ approach harnesses biocatalytic pathways, in the absence of living cells, to synthesize small molecules used as pharmaceuticals, nutraceuticals, flavors, and fragrances, but also specific commodity chemicals and fuels. To clarify terminology, we introduce the new terms ‘exozymes’ and ‘exozyme systems’ as unambiguous descriptors for ‘cell-free biomanufacturing.’