Thiol-disulfide oxidoreductases are essential for the production of the lantibiotic sublancin 168
Thiol-disulfide oxidoreductases are essential for the production of the lantibiotic sublancin 168
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DOI：
10.1074/jbc.m201158200
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发表时间：
2002-05-10
影响因子：
4.8
通讯作者：
van Dijl, JM
中科院分区：
文献类型：
--
作者：
Dorenbos, R;Stein, T;van Dijl, JM
巯基-二硫键氧化还原酶是从细胞质输出的蛋白质中形成二硫键所必需的。已在革兰氏阳性真杆菌枯草芽孢杆菌中鉴定出四种这种类型的酶，称为BdbA、BdbB、BdbC和BdbD。BdbC和BdbD已被证明是至关重要的蛋白质的折叠所需的DNA摄取在自然的感受态。与此相反，迄今为止还没有功能被分配给BdbA和BdbB蛋白。bdbA和bdbB基因位于一个操纵子中，该操纵子还含有指定lantibiotic sublancin 168和ATP结合盒转运蛋白SunT的基因。有趣的是，sublancin 168含有两个二硫键。目前的研究表明，SunT和BdbB，而不是BdbA，是生产活性sublancin 168所必需的。此外，BdbB paraminBdbC至少部分能够在亚兰菌素168生产中替代BdbB。这些观察结果表明，前所未有的参与硫醇-二硫化物氧化还原酶的肽抗生素的合成。值得注意的是，BdbB不能在感受态发育中补充BdbC，表明这两种密切相关的硫醇-二硫键氧化还原酶具有不同但部分重叠的底物特异性。
Thiol-disulfide oxidoreductases are required for disulfide bond formation in proteins that are exported from the cytoplasm. Four enzymes of this type, termed BdbA, BdbB, BdbC, and BdbD, have been identified in the Gram-positive eubacterium Bacillus subtilis. BdbC and BdbD have been shown to be critical for the folding of a protein required for DNA uptake during natural competence. In contrast, no function has been assigned so far to the BdbA and BdbB proteins. The bdbA and bdbB genes are located in one operon that also contains the genes specifying the lantibiotic sublancin 168 and the ATP-binding cassette transporter SunT. Interestingly sublancin 168 contains two disulfide bonds. The present studies demonstrate that SunT and BdbB, but not BdbA, are required for the production of active sublancin 168. In addition, the BdbB paralogue BdbC is at least partly able to replace BdbB in sublancin 168 production. These observations show the unprecedented involvement of thiol-disulfide oxidoreductases in the synthesis of a peptide antibiotic. Notably BdbB cannot complement BdbC in competence development, showing that these two closely related thiol-disulfide oxidoreductases have different, but partly overlapping, substrate specificities.