Issue 2, 2014

Inteins: nature's gift to protein chemists

Abstract

Inteins are auto-processing domains found in organisms from all domains of life. These proteins carry out a process known as protein splicing, which is a multi-step biochemical reaction comprised of both the cleavage and formation of peptide bonds. While the endogenous substrates of protein splicing are specific essential proteins found in intein-containing host organisms, inteins are also functional in exogenous contexts and can be used to chemically manipulate virtually any polypeptide backbone. Given this, protein chemists have exploited various facets of intein reactivity to modify proteins in myriad ways for both basic biological research as well as potential therapeutic applications. Here, we review the intein field, first focusing on the biological context and phylogenetic diversity of inteins, followed by a description of intein structure and biochemical function. Finally, we discuss prevalent intein-based technologies, focusing on their applications in chemical biology, followed by persistent caveats of intein chemistry and approaches to alleviate these shortcomings. The findings summarized herein describe two and a half decades of research, leading from a biochemical curiosity to the development of powerful protein engineering tools.

Graphical abstract: Inteins: nature's gift to protein chemists

Article information

Article type
Perspective
Submitted
24 Oct 2013
Accepted
27 Nov 2013
First published
10 Dec 2013

Chem. Sci., 2014,5, 446-461

Inteins: nature's gift to protein chemists

N. H. Shah and T. W. Muir, Chem. Sci., 2014, 5, 446 DOI: 10.1039/C3SC52951G

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