Insertions and deletions in protein evolution and engineering

作者：Simone Savino, Tom Desmet, Jorick Franceus · 发表于：Biotechnology Advances · 年份：2022 · DOI：10.1016/j.biotechadv.2022.108010 · 被引用次数：92 · 研究领域：Genomics and Phylogenetic Studies、RNA and protein synthesis mechanisms、Machine Learning in Bioinformatics

Protein evolution or engineering studies are traditionally focused on amino acid substitutions and the way these contribute to fitness. Meanwhile, the insertion and deletion of amino acids is often overlooked, despite being one of the most common sources of genetic variation. Recent methodological advances and successful engineering stories have demonstrated that the time is ripe for greater emphasis on these mutations and their understudied effects. This review highlights the evolutionary importance and biotechnological relevance of insertions and deletions (indels). We provide a comprehensive overview of approaches that can be employed to include indels in random, (semi)-rational or computational protein engineering pipelines. Furthermore, we discuss the tolerance to indels at the structural level, address how domain indels can link the function of unrelated proteins, and feature studies that illustrate the surprising and intriguing potential of frameshift mutations.