Faculty of Mathematics and Computer Science, University of Wrocław, ul. F. Joliot-Curie 15, 50-383 Wrocław, Poland.
Department of Bioinformatics and Genomics, Faculty of Biotechnology, University of Wrocław, ul F. Joliot-Curie 14a, 50-383 Wrocław, Poland.
Genetics. 2021 May 17;218(1). doi: 10.1093/genetics/iyab040.
Reprogramming of the standard genetic code to include non-canonical amino acids (ncAAs) opens new prospects for medicine, industry, and biotechnology. There are several methods of code engineering, which allow us for storing new genetic information in DNA sequences and producing proteins with new properties. Here, we provided a theoretical background for the optimal genetic code expansion, which may find application in the experimental design of the genetic code. We assumed that the expanded genetic code includes both canonical and non-canonical information stored in 64 classical codons. What is more, the new coding system is robust to point mutations and minimizes the possibility of reversion from the new to old information. In order to find such codes, we applied graph theory to analyze the properties of optimal codon sets. We presented the formal procedure in finding the optimal codes with various number of vacant codons that could be assigned to new amino acids. Finally, we discussed the optimal number of the newly incorporated ncAAs and also the optimal size of codon groups that can be assigned to ncAAs.
重新编程标准遗传密码以包含非规范氨基酸 (ncAAs) 为医学、工业和生物技术开辟了新的前景。有几种编码工程方法，可用于在 DNA 序列中存储新的遗传信息并产生具有新特性的蛋白质。在这里，我们为最佳遗传密码扩展提供了理论背景，这可能在遗传密码的实验设计中找到应用。我们假设扩展的遗传密码包括存储在 64 个经典密码子中的规范和非规范信息。更重要的是，新的编码系统对点突变具有鲁棒性，并最大程度地减少了从新信息恢复到旧信息的可能性。为了找到这样的代码，我们应用图论来分析最优密码子集的性质。我们提出了一种正式的程序，用于找到具有各种空位密码子的最优代码，这些空位密码子可以分配给新的氨基酸。最后，我们讨论了新掺入的 ncAAs 的最佳数量以及可以分配给 ncAAs 的最佳密码子组大小。
