ThioFinder: a web-based tool for the identification of thiopeptide gene clusters in DNA sequences.

ThioFinder: a web-based tool for the identification of thiopeptide gene clusters in DNA sequences.
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ThioFinder:一种基于网络的工具,用于识别 DNA 序列中的硫肽基因簇

DOI:
10.1371/journal.pone.0045878
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Ou HY
Ou HY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li J;Qu X;He X;Duan L;Wu G;Bi D;Deng Z;Liu W;Ou HY

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硫肽是一类不断增长的富硫、高度修饰的杂环肽,其主要对革兰氏阳性细菌包括各种耐药病原体具有活性。最近的研究还发现,许多硫肽抑制人类癌细胞的增殖,进一步扩大了其在临床上的应用潜力。硫肽生物合成共享一个共同的范例,具有核糖体合成的前体肽和保守的翻译后修饰,以提供一个特征性的核心系统,但在定制以提供单个成员方面有所不同。利用细菌DNA序列信息的不断增加,鉴定新的硫肽基因簇,有助于发现新的硫肽,富集独特的生物合成元件,应用组合生物合成原理生产新的药物先导物。在这项研究中,我们已经开发了一个基于Web的工具Thioblasts快速识别硫肽生物合成基因簇的DNA序列,使用轮廓隐马尔可夫模型的方法。在先前未知的生产微生物的测序细菌基因组中发现了54个新的假定硫肽生物合成基因簇。Thiopeptides完全由开放访问数据库ThioBase支持,该数据库包含99种已知硫肽的足够信息,包括化学结构、生物活性、生产生物体和生物合成基因(簇)沿着相关基因组(如果可用)。Thiopeptide网站为研究人员提供了独特的资源和极大的灵活性,用于硫肽生物合成基因簇的序列分析。硫代巴比妥可在http://db-mml.sjtu.edu.cn/ThioFinder/上免费获得。
Thiopeptides are a growing class of sulfur-rich, highly modified heterocyclic peptides that are mainly active against Gram-positive bacteria including various drug-resistant pathogens. Recent studies also reveal that many thiopeptides inhibit the proliferation of human cancer cells, further expanding their application potentials for clinical use. Thiopeptide biosynthesis shares a common paradigm, featuring a ribosomally synthesized precursor peptide and conserved posttranslational modifications, to afford a characteristic core system, but differs in tailoring to furnish individual members. Identification of new thiopeptide gene clusters, by taking advantage of increasing information of DNA sequences from bacteria, may facilitate new thiopeptide discovery and enrichment of the unique biosynthetic elements to produce novel drug leads by applying the principle of combinatorial biosynthesis. In this study, we have developed a web-based tool ThioFinder to rapidly identify thiopeptide biosynthetic gene cluster from DNA sequence using a profile Hidden Markov Model approach. Fifty-four new putative thiopeptide biosynthetic gene clusters were found in the sequenced bacterial genomes of previously unknown producing microorganisms. ThioFinder is fully supported by an open-access database ThioBase, which contains the sufficient information of the 99 known thiopeptides regarding the chemical structure, biological activity, producing organism, and biosynthetic gene (cluster) along with the associated genome if available. The ThioFinder website offers researchers a unique resource and great flexibility for sequence analysis of thiopeptide biosynthetic gene clusters. ThioFinder is freely available at http://db-mml.sjtu.edu.cn/ThioFinder/.
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发表时间: 2011-04-01
期刊: Bioinformatics (Oxford, England)
影响因子: --
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