Effect of amino acid substitutions in conserved residues in the leader peptide on biosynthesis of the lantibiotic mutacin II
Effect of amino acid substitutions in conserved residues in the leader peptide on biosynthesis of the lantibiotic mutacin II
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DOI：
10.1111/j.1574-6968.2001.tb10511.x
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发表时间：
2001-02-20
影响因子：
2.1
通讯作者：
Caufield, PW
中科院分区：
文献类型：
--
作者：
Chen, P;Qi, FX;Caufield, PW
由变形链球菌T8产生的羊毛硫抗生素突变蛋白II是一种核糖体合成的肽抗生素，其含有硫醚氨基酸，如羊毛硫氨酸和甲基羊毛硫氨酸，作为翻译后修饰的结果。突变蛋白II前导肽序列与AII类羊毛硫抗生素前导肽共有许多相同的氨基酸残基。为了研究这些保守残基在产生活性抗微生物突变素中的作用，通过定点诱变产生15个突变。这些取代的效果从没有效果到完全阻断。突变G-1A、G-2A、I-4D和L-7K完全阻断成熟变蛋白的产生。其他突变（I-4V、L-7M、E-8D、S-11 T/A、V-12 I/A和E-13 D）对突变蛋白的产生没有可检测的影响。Glu-8变为Lys、瓦尔-12变为Leu、Glu-13变为Lys分别使突变蛋白产生水平降低至野生型的约75%、50%和10%。因此，我们的数据表明，这些保守的残基中的一些是必不可少的突变蛋白的生物合成，而其他的是重要的最佳生物合成速率。(C)2001年，欧洲微生物学会联合会。由Elsevier Science B.V.出版，版权所有。
The lantibiotic mutacin II, produced by Streptococcus mutans T8, is a ribosomally synthesized peptide antibiotic that contains thioether amino acids such as lanthionine and methyllanthionine as a result of post-translational modifications. The mutacin II leader peptide sequence shares a number of identical amino acid residues with class AII lantibiotic leader peptides. To study the role of these conservative residues in the production of active antimicrobial mutacin, 15 mutations were generated by site-directed mutagenesis. The effects of these substitutions vary from no effect to complete block-out. Mutations G-1A, G-2A, I-4D, and L-7K completely blocked the production of mature mutacin. Other mutations (I-4V, L-7M, E-8D, S-11T/A, V-12I/A, and E-13D) had no detectable effect on mutacin production. The changes of Glu-8 to Lys, Val-12 to Leu, Glu-13 to Lys reduced the mutacin production level to about 75%, 50%, and 10% of the wild-type, respectively. Thus, our data indicated that some of these conserved residues are essential for the mutacin biosynthesis, whereas others are important for optimal biosynthesis rates. (C) 2001 Federation of European Microbiological societies. published by Elsevier science B.V. All rights reserved.