Full-length title: NRPPUR database search and in vitro analysis identify an NRPS-PKS biosynthetic gene cluster with a potential antibiotic effect
Full-length title: NRPPUR database search and in vitro analysis identify an NRPS-PKS biosynthetic gene cluster with a potential antibiotic effect
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DOI：
10.1186/s12859-018-2479-5
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发表时间：
2018-12-03
影响因子：
3
通讯作者：
Merhej, Vicky
中科院分区：
文献类型：
--
作者：
Fritz, Shirley;Rajaonison, Andriamiharimamy;Merhej, Vicky
背景对抗生素耐药性的日益增长的担忧迫使制药业寻找新的抗菌剂。基因组序列的可获得性使得计算机挖掘成为发现具有抗生素作用的天然产物的重要工具。结果NRPPUR(非核糖体肽和聚酮URMITE)是一种新的生物信息学工具，用于检测细菌基因组中的多酮和非核糖体肽基因簇(PKS和NRPS)。NRPPUR数据库是通过组装到目前为止用电子方法鉴定的所有3505个可用的NRPS-PKS序列来本地构建的，其中164个生物合成基因簇(BGC)来自已发表的文献，这些文献已经证明了体外抗菌活性。使用NRPPUR对49个肠道细菌基因组进行的电子分析使人们有可能识别出91个BGC，其中包括89个以前从未描述过的簇。平均而言，人类肠道细菌基因组投入了近0.8%(1.4%S.D.)其中苦味芽孢杆菌、马西里链霉菌和枯草杆菌基因组分别占其基因组的8.4%、3.6%和3.15%。结论p id=par3 NRPPUR对多种革兰氏阳性菌和革兰氏阴性菌均有抗菌活性。结论p id=par3 NRPPUR是一种非常有用的工具，可用于初步筛选具有潜在抗菌活性的菌种，人类微生物区系可能成为未来抗菌药物新发现的来源。进一步探索这一生态位和其他生态位，再加上高通量的抗菌活性筛选，应该是可以预见的。
BackgroundGrowing concern about the emergence of antibiotic resistance is compelling the pharmaceutical industry to search for new antimicrobial agents. The availability of genome sequences has enabled the development of computational mining as an important tool in the discovery of natural products with antibiotic effect.ResultsNRPPUR (Non-Ribosomal Peptide and Polyketide Urmite) is a new bioinformatic tool that was created to detect polyketides and non-ribosomal peptide gene clusters (PKS and NRPS) in bacterial genomes using the rpsBlast program. The NRPPUR database was constructed locally by assembling all 3505 available sequences of NRPS-PKS that have been identified by in silico approaches to date, with 164 Biosynthetic Gene Clusters (BGCs) derived from the published literature that have demonstrated antimicrobial activity in vitro. The in silico analysis of 49 intestinal human bacterial genomes using the NRPPUR made it possible to identify 91 BGCs including 89 clusters that had never previously been described. On average, intestinal human bacterial genomes devote nearly 0.8% (1.4% s.d.) of their genome to NRPS/PKS biosynthesis, with Bacillus vallismortis, Streptomyces massiliensis and Bacillus subtilis genomes apportioning 8.4, 3.6 and 3.15% of their genomes, respectively. When using the cross-streak method, S. massiliensis displayed antibacterial activity against many Gram-positive and negative bacteria including methicillin-resistant Staphylococcus aureus (MRSA).Conclusions p id=Par3 NRPPUR has proven to be a very useful tool for the primary in silico selection of species with potential antimicrobial activity and human microbiota could be the future source of new antimicrobial discoveries. Further exploration of this and other ecological niches, coupled with high-throughput antibacterial activity screening should be envisaged.