Molecular beacons to identify gifted microbes for genome mining

Molecular beacons to identify gifted microbes for genome mining
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DOI:
10.1038/ja.2017.1
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发表时间:
2017-05-01
影响因子:
3.3
通讯作者:
Baltz, Richard H.
Baltz, Richard H.
中科院分区:
医学4区
文献类型:
--
作者:
Baltz, Richard H.

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微生物基因组挖掘是一项很有前途的技术,正在振兴天然产物的发现。现在有充分的证据表明,许多具有大基因组的细菌,特别是放线菌,编码的次级代谢物(SM)比以前从其表达的次级代谢物组中已知的要多得多。有有效的生物信息学工具来计算SM的数量和性质,并确定完成的微生物基因组的总编码能力。然而,这些方法不能很好地转化为草图基因组,特别是对于含有非核糖体肽合成酶(NRPS)或I型聚酮合酶(PKS-I)大基因的大SM基因簇,其易于片段化和错误组装。需要小分子信标来评估NRPS、PKS-I和混合NRPS/PKS-I途径的数量和种类。在这份报告中,我表明,串联肽基载体蛋白-硫酯酶双结构域和酰基载体蛋白-硫酯酶双结构域可以作为多探针来调查完成或草案基因组,以估计NRPS,PKS-I和混合NRPS/PKS-I基因簇的数量,以鉴定有天赋的放线菌。
Microbial genome mining is a promising technology that is revitalizing natural product discovery. It is now well documented that many bacteria with large genomes, particularly actinomycetes, encode many more secondary metabolites (SMs) than was previously known from their expressed secondary metabolomes. There are effective bioinformatics tools for counting the numbers and nature of SMs, and determining the total coding capacity from finished microbial genomes. However, these methods do not translate well to draft genomes, particularly for large SM gene clusters that contain nonribosomal peptide synthetase (NRPS) or type I polyketide synthase (PKS- I) mega-genes which are prone to fragmentation and misassembly. Small molecular beacons are required to assess the numbers and variety of NRPS, PKS- I and mixed NRPS/PKS-I pathways. In this report, I show that concatenated peptidyl carrier protein-thioesterase di-domains and acyl carrier protein-thioesterase di-domains can be used as multi-probes to survey finished or draft genomes to estimate the numbers of NRPS, PKS- I and mixed NRPS/PKS-I gene clusters to identify gifted actinomycetes.