Exozymes for Biomanufacturing: Toward Clarity and Precision in the Cell-Free Space
- 1. XoZymes, Inc., Monrovia, California, USA.
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2.
California Institute of Technology
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3.
National Renewable Energy Laboratory
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4.
University of Colorado Boulder
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5.
University of California, Los Angeles
- 6. Sepia Biosciences, LLC, San Francisco, California, USA.
- 7. Lalonde Consultancy, San Mateo, California, USA.
- 8. Ferment Co., Los Angeles, California, USA.
Abstract
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.
Copyright and License (English)
© The Author(s) 2025. Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Funding (English)
Work at eXoZymes Inc. was in part supported by the U.S. Department of Energy’s Office of Energy Efficiency and Renewable Energy (EERE) under the Conversion Research and Development Program award number DE-EE0011113 and received additional support by National Institute of General Medical Sciences of the National Institutes of Health under award number 1R43GM153108-01. This work was authored in part by the National Renewable Energy Laboratory, operated by Alliance for Sustainable Energy, LLC, for the U.S. Department of Energy (DOE) under Contract No. DE-AC36-08GO28308. Funding provided by U.S. Department of Energy Office of Energy Efficiency and Renewable Energy under the Cell Free and Immobilization Technologies initiative.
Additional Information
A.B., B.V., J.M.B., P.H.O., E.V., M.H., L.G., and T.P.K. are employees of eXoZymes, Inc., a company that commercializes enzyme and cell-free technologies. J.U.B., T.P.K., and P.H.O. are scientific co-founders of eXoZymes, Inc., and J.U.B. and J.L. serve on its board of directors. The terms exozymes and exozyme systems introduced in this article are intended to provide a clearer framework for the field and are not proprietary to eXoZymes, Inc. These terms are freely available for use by the broader scientific community, and no trademarks have been filed.
Acknowledgement
The authors would like to thank Emily Roberts, Berge Hagopian, Chris Rabot, and Miyoshi Haruta for their valuable input during the writing process.
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Additional details
- Office of Energy Efficiency and Renewable Energy
- Conversion Research and Development Program DE-EE0011113
- National Institute of General Medical Sciences
- 1R43GM153108-01
- Available
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2025-04-17Published online
- Caltech groups
- Division of Biology and Biological Engineering (BBE)
- Publication Status
- Published