Genomics and the ancient origins of the daptomycin biosynthetic gene cluster
Genomics and the ancient origins of the daptomycin biosynthetic gene cluster
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DOI：
10.1038/ja.2010.82
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发表时间：
2010-08-01
影响因子：
3.3
通讯作者：
Baltz, Richard H.
中科院分区：
文献类型：
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作者：
Baltz, Richard H.
达托霉素是一种临床上有用的脂肽抗生素，由玫瑰孢链霉菌产生。该抗生素通过非核糖体肽合成酶（NRPS）机制组装而成，环化十三肽含有三种非蛋白原性L-氨基酸：鸟氨酸（Orn）、3-甲基谷氨酸（3mGlu）和犬尿氨酸（Kyn）。达托霉素还含有三种 D-氨基酸。编码参与 3mGlu 和 Kyn 形成的蛋白质的两个基因没有已知的直系同源物，因此它们是在新测序的放线菌基因组中寻找达托霉素样基因簇的良好探针。最近对这些基因的研究揭示了绿色糖单孢菌（农民肺病的病原体）中存在类似达托霉素的基因簇。 S. viridis 的基因组为 4.3 Mb，大约是链霉菌基因组大小的一半。对其他 NRPS 和聚酮合酶 (PKS) 基因的搜索显示，S. virichs 中仅存在一种其他 NRPS 基因，而没有 PKS 基因。 S. viridis 和 S. Roseosporus 中的直向同源脂肽生物合成基因和基因产物与最后一个共同祖先存在很大差异，该祖先可以追溯到 10 亿多年前进化的途径。抗生素杂志 (2010) 63, 506-511。 doi 10 1038/ja 2010 82，2010 年 7 月 21 日在线发布
Daptomycin is a clinically useful lipopeptide antibiotic produced by Streptomyces roseosporus. The antibiotic is assembled by a nonribosomal peptide synthetase (NRPS) mechanism, and the cyclized tridecapeptide contains three non-proteinogenic L-amino acids: ornithine (Orn), 3-methyl-glutamic acid (3mGlu) and kynurinine (Kyn). Daptomycin also has three D-amino acids. The two genes that encode proteins involved in the formation of 3mGlu and Kyn have no known orthologs, and hence they are good probes to search for daptomycin-like gene clusters among newly sequenced actinomycete genomes. A recent search with these genes revealed a daptomycin-like gene cluster in Saccharomonospora viridis, a causative agent for farmer's lung disease. S. viridis has a genome of 4.3 Mb, which is about one half the size of Streptomyces genomes. Searches for other NRPS and polyketide synthase (PKS) genes revealed only one other NRPS gene and no PKS genes in S. virichs. The orthologous lipopeptide biosynthetic genes and gene products in S. viridis and S. roseosporus have diverged extensively from a last common ancestor dating back to a pathway that had evolved over 1 billion years ago. The Journal of Antibiotics (2010) 63, 506-511. doi 10 1038/ja 2010 82, published online 21 July 2010