PREPEPTIDE SEQUENCE OF EPIDERMIN, A RIBOSOMALLY SYNTHESIZED ANTIBIOTIC WITH 4 SULFIDE-RINGS
PREPEPTIDE SEQUENCE OF EPIDERMIN, A RIBOSOMALLY SYNTHESIZED ANTIBIOTIC WITH 4 SULFIDE-RINGS
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DOI：
10.1038/333276a0
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发表时间：
1988-05-19
期刊：
影响因子：
64.8
通讯作者：
JUNG, G
中科院分区：
文献类型：
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作者：
SCHNELL, N;ENTIAN, KD;JUNG, G
迄今为止，尚未解释诸如乳链菌肽等大型多肽抗生素生物合成的遗传基础。我们在这里展示了编码来自表皮葡萄球菌的抗生素 epidermin1,2 的结构基因 epiA 位于 54 KB 的质粒上，并编码 52 个氨基酸的前肽，该前肽被加工成四环 21 肽酰胺抗生素。表皮蛋白的成熟序列对应于前表皮蛋白的 C 端 22 肽片段，并包含前体氨基酸 Ser、Thr 和 Cys，从中衍生出不常见的氨基酸成分。亲脂性较高的表皮在 N 末端片段 –30 至 –1 的 Arg–1 和 Ile+1 之间的亲水转角处被裂解，这可能呈现部分两亲性的 a 螺旋构象。我们认为，N 末端（–30 至 –1）在修饰反应过程中发挥协同作用，并在抗生素裂解和分泌之前防止成熟表皮对生产菌株的毒性。
The genetic basis for the biosynthesis of large polypeptide antibiotics such as nisin has not been explained so far. We show here that the structural geneepiA encoding the antibiotic epidermin1,2fromStaphylococcus epidermidisis located on a 54-kilobase plas-mid and codes for a 52-amino-acid prepeptide, which is processed to the tetracyclic 21-peptide amide antibiotic. The mature sequence of epidermin corresponds to the C-terminal 22-peptide segment of pre-epidermin and contains the precursor amino acids Ser, Thr and Cys, from which the unusual amino-acid constituents are derived. The more lipophilic epidermin is cleaved at a hydrophilic turn between Arg–1and Ile+1from the N-terminal segment –30 to –1, which probably assumes a partially amphiphilic a-helix conformation. We propose that the N-terminus (–30 to –1) plays a cooperative role during modification reactions and prevents toxicity of the mature epidermin to the producing strain before the antibiotic is cleaved off and secreted.