Biotechnology and Bioprocess Engineering 2023; 28(6): 905-921  
Cell-free Biosynthesis of Peptidomimetics
Kanghun Lee, Jessica A. Willi, Namjin Cho, Inseon Kim, Michael C. Jewett, and Joongoo Lee
Kanghun Lee, Inseon Kim, Joongoo Lee
School of Interdisciplinary Bioscience and Bioengineering (I-Bio), Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea
Jessica A. Willi, Michael C. Jewett
Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA
Namjin Cho, Joongoo Lee*
Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea
Tel: +82-54-279-2269; Fax: +82-54-279-5528
E-mail: jgoolee@postech.ac.kr
Michael C. Jewett*
Center for Synthetic Biology, Northwestern University, Evanston, IL 60208, USA
Tel: +1-847-467-5007; Fax: +1-847-491-3728
E-mail: m-jewett@northwestern.edu
Kanghun Lee and Jessica A. Willi contributed equally to this work.
Received: September 8, 2022; Revised: October 16, 2022; Accepted: November 13, 2022; Published online: December 31, 2023.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
A wide variety of peptidomimetics (peptide analogs) possessing innovative biological functions have been brought forth as therapeutic candidates through cell-free protein synthesis (CFPS) systems. A key feature of these peptidomimetic drugs is the use of non-canonical amino acid building blocks with diverse biochemical properties that expand functional diversity. Here, we summarize recent technologies leveraging CFPS platforms to expand the reach of peptidomimetic drugs. We also offer perspectives on engineering the translational machinery that may open new opportunities for expanding genetically encoded chemistry to transform drug discovery practice beyond traditional boundaries.
Keywords: peptidomimetics, cell-free protein synthesis systems, non-canonical amino acids, translational machinery


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