Characterization of the 'pristinamycin supercluster' of Streptomyces pristinaespiralis.

Characterization of the 'pristinamycin supercluster' of Streptomyces pristinaespiralis.
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DOI:
10.1111/j.1751-7915.2010.00213.x
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发表时间:
2011-03
影响因子:
5.7
通讯作者:
Schinko E
Schinko E
中科院分区:
工程技术2区
文献类型:
--
作者:
Mast Y;Weber T;Gölz M;Ort-Winklbauer R;Gondran A;Wohlleben W;Schinko E

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普那霉素是由Streptomyces pristinaespiralis Pr11产生的,是一种链阳性抗生素,由两种化学上不相关的化合物普那霉素I和普那霉素II组成。这些化合物的半合成衍生物在人类医学中用作抗甲氧西林耐药金黄色葡萄球菌菌株的治疗剂。只有部分序列的普那霉素生物合成基因簇已被先前报道。为了完成序列,从S. pristinaespiralisPr11基因文库并测序。推导出簇的边界,将簇大小限制在约210 kb。 在簇的中心区域,鉴定了以前未知的普那霉素生物合成基因。结合目前和以前确定的序列信息,我们建议,所有必需的普那霉素生物合成基因包括在210 kb的区域。 建立了普那霉素生物合成途径。此外,普那霉素基因簇被发现散布由一个隐蔽的次级代谢物簇,这可能是编码的糖基化的芳香聚酮。基因失活实验表明,该簇对普那霉素的产生没有影响。总的来说,这项工作提供了新的见解原始霉素的生物合成和原始霉素基因区的独特的遗传组织,这是迄今为止已知的最大的抗生素“超簇”。
Pristinamycin, produced by Streptomyces pristinaespiralis Pr11, is a streptogramin antibiotic consisting of two chemically unrelated compounds, pristinamycin I and pristinamycin II. The semi‐synthetic derivatives of these compounds are used in human medicine as therapeutic agents against methicillin‐resistant Staphylococcus aureus strains. Only the partial sequence of the pristinamycin biosynthetic gene cluster has been previously reported. To complete the sequence, overlapping cosmids were isolated from a S. pristinaespiralis Pr11 gene library and sequenced. The boundaries of the cluster were deduced, limiting the cluster size to approximately 210 kb. In the central region of the cluster, previously unknown pristinamycin biosynthetic genes were identified. Combining the current and previously identified sequence information, we propose that all essential pristinamycin biosynthetic genes are included in the 210 kb region. A pristinamycin biosynthetic pathway was established. Furthermore, the pristinamycin gene cluster was found to be interspersed by a cryptic secondary metabolite cluster, which probably codes for a glycosylated aromatic polyketide. Gene inactivation experiments revealed that this cluster has no influence on pristinamycin production. Overall, this work provides new insights into pristinamycin biosynthesis and the unique genetic organization of the pristinamycin gene region, which is the largest antibiotic ‘supercluster’ known so far.
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