Chemoenzymatic Semisynthesis of Proteins

Robert E. Thompson, Tom W. Muir

Research output: Contribution to journalReview articlepeer-review

137 Scopus citations


Protein semisynthesis - defined herein as the assembly of a protein from a combination of synthetic and recombinant fragments - is a burgeoning field of chemical biology that has impacted many areas in the life sciences. In this review, we provide a comprehensive survey of this area. We begin by discussing the various chemical and enzymatic methods now available for the manufacture of custom proteins containing noncoded elements. This section begins with a discussion of methods that are more chemical in origin and ends with those that employ biocatalysts. We also illustrate the commonalities that exist between these seemingly disparate methods and show how this is allowing for the development of integrated chemoenzymatic methods. This methodology discussion provides the technical foundation for the second part of the review where we cover the great many biological problems that have now been addressed using these tools. Finally, we end the piece with a short discussion on the frontiers of the field and the opportunities available for the future.

Original languageEnglish (US)
Pages (from-to)3051-3126
Number of pages76
JournalChemical Reviews
Issue number6
StatePublished - Mar 25 2020

All Science Journal Classification (ASJC) codes

  • General Chemistry


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