Analysis of the distribution of functionally relevant rare codons
Analysis of the distribution of functionally relevant rare codons
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DOI：
10.1186/1471-2164-9-207
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发表时间：
2008-05-05
期刊：
影响因子：
4.4
通讯作者：
Pleiss, Juergen
中科院分区：
文献类型：
--
作者：
Widmann, Michael;Clairo, Marie;Pleiss, Juergen
背景资料：用更频繁的密码子替换稀有密码子是异源基因表达中常用的方法，以增加蛋白质产量。然而，在某些情况下，这些取代导致蛋白质溶解度或活性的降低。为了预测这些功能相关的稀有密码子，开发了一种基于同源蛋白质家族的多序列比对分析的方法，结果：该方法成功地预测了实验确定的脂肪酸结合蛋白和氯霉素乙酰转移酶的功能相关密码子。然而，16个同源的蛋白质家族属于α/β水解酶倍的分析表明，功能罕见的密码子共享没有共同的位置，在三级和二级structure.Conclusion：同源蛋白质家族的多序列比对的系统分析，可以用来预测罕见的密码子与蛋白质表达的潜在影响。我们的分析表明，大多数基因含有至少一个推定的稀有密码子丰富的区域。在通过用更频繁的密码子交换稀有密码子来改善蛋白质表达的方法中，应该排除位于这些区域附近的稀有密码子。
Background: The substitution of rare codons with more frequent codons is a commonly applied method in heterologous gene expression to increase protein yields. However, in some cases these substitutions lead to a decrease of protein solubility or activity. To predict these functionally relevant rare codons, a method was developed which is based on an analysis of multisequence alignments of homologous protein families.Results: The method successfully predicts functionally relevant codons in fatty acid binding protein and chloramphenicol acetyltransferase which had been experimentally determined. However, the analysis of 16 homologous protein families belonging to the alpha/beta hydrolase fold showed that functionally rare codons share no common location in respect to the tertiary and secondary structure.Conclusion: A systematic analysis of multisequence alignments of homologous protein families can be used to predict rare codons with a potential impact on protein expression. Our analysis showed that most genes contain at least one putative rare codon rich region. Rare codons located near to those regions should be excluded in an approach of improving protein expression by an exchange of rare codons by more frequent codons.