Evolutionary investigations of the biosynthetic diversity in the skin microbiome using lsaBGC.
Evolutionary investigations of the biosynthetic diversity in the skin microbiome using lsaBGC.
复制标题
DOI：
10.1099/mgen.0.000988
复制
发表时间：
2023-04
影响因子：
3.9
通讯作者：
Kalan, Lindsay R.
中科院分区：
文献类型：
--
作者：
Salamzade, Rauf;Cheong, J. Z. Alex;Sandstrom, Shelby;Swaney, Mary Hannah;Stubbendieck, Reed M.;Starr, Nicole Lane;Currie, Cameron R.;Singh, Anne Marie;Kalan, Lindsay R.
关键词：
细菌次生代谢物是由生物合成基因簇（bgc）编码的酶合成的，可以作为微生物组稳态的基础，并作为商业化产品，历史上从一组精选的分类群中开采出来。虽然进化方法已被证明有利于在实验表征工作中优先考虑bgc，以发现新的天然产物，但专为焦点分类群中bgc的比较和进化分析而设计的生物信息学工具有限。因此，我们开发了BGCs的谱系特异性分析（lsaBGC; https://github.com/Kalan-Lab/lsaBGC），以帮助探索任何感兴趣的细菌分类群中BGCs同源分组，基因簇家族（GCFs）的微多样性和进化趋势。lsaBGC能够快速、直接地鉴定基因组中的gcf，计算BGC基因的进化统计和保守性，并建立一个框架，允许通过宏基因组探索来挖掘基本分辨率的新变异。通过将该套件应用于皮肤微生物组中常见的四个属，我们揭示了其bgc的进化和多样性的新见解。我们发现，在金黄色葡萄球菌中，毒力相关的类胡萝卜素葡萄黄素的BGC在葡萄球菌属中普遍存在。虽然一个编码葡萄黄质生物合成的GCF显示了质粒介导的物种间水平基因转移（HGT）的证据，但另一个GCF似乎在皮肤相关葡萄球菌的亚支系中垂直传播。此外，后者的GCF在金黄色葡萄球菌中保存良好，在大多数表皮葡萄球菌中已经丢失，表皮葡萄球菌是人类皮肤上最常见的葡萄球菌，也被认为是共生的。我们还从硬脂棒状杆菌复合体的bgc中鉴定出数千个新的单核苷酸变异（snv），这是一个狭窄的多物种分支，其特征是健康皮肤微生物群中最普遍的棒状杆菌。尽管位于保守位点前5个百分点的新snv对应同同义词变化的可能性约为10倍，但lsaBGC发现的snv违背了这一趋势，并被预测为功能关键酶结构域内氨基酸变化的基础。最终，除了支持bgc的进化研究之外，lsaBGC还提供了重要的功能来帮助发现或直接修改天然产物。
Bacterial secondary metabolites, synthesized by enzymes encoded in biosynthetic gene clusters (BGCs), can underlie microbiome homeostasis and serve as commercialized products, which have historically been mined from a select group of taxa. While evolutionary approaches have proven beneficial for prioritizing BGCs for experimental characterization efforts to uncover new natural products, dedicated bioinformatics tools designed for comparative and evolutionary analysis of BGCs within focal taxa are limited. We thus developed lineage specific analysis of BGCs (lsaBGC; https://github.com/Kalan-Lab/lsaBGC) to aid exploration of microdiversity and evolutionary trends across homologous groupings of BGCs, gene cluster families (GCFs), in any bacterial taxa of interest. lsaBGC enables rapid and direct identification of GCFs in genomes, calculates evolutionary statistics and conservation for BGC genes, and builds a framework to allow for base resolution mining of novel variants through metagenomic exploration. Through application of the suite to four genera commonly found in skin microbiomes, we uncover new insights into the evolution and diversity of their BGCs. We show that the BGC of the virulence-associated carotenoid staphyloxanthin in Staphylococcus aureus is ubiquitous across the genus Staphylococcus . While one GCF encoding the biosynthesis of staphyloxanthin showcases evidence for plasmid-mediated horizontal gene transfer (HGT) between species, another GCF appears to be transmitted vertically amongst a sub-clade of skin-associated Staphylococcus . Further, the latter GCF, which is well conserved in S. aureus , has been lost in most Staphylococcus epidermidis , which is the most common Staphylococcus species on human skin and is also regarded as a commensal. We also identify thousands of novel single-nucleotide variants (SNVs) within BGCs from the Corynebacterium tuberculostearicum sp. complex, a narrow, multi-species clade that features the most prevalent Corynebacterium in healthy skin microbiomes. Although novel SNVs were approximately 10 times as likely to correspond to synonymous changes when located in the top five percentile of conserved sites, lsaBGC identified SNVs that defied this trend and are predicted to underlie amino acid changes within functionally key enzymatic domains. Ultimately, beyond supporting evolutionary investigations of BGCs, lsaBGC also provides important functionalities to aid efforts for the discovery or directed modification of natural products.
登录
查看更多内容
DOI：
10.1093/bioadv/vbab016
发表时间：
2021
期刊：
Bioinformatics advances
影响因子：
--
作者：
通讯作者：
--
影响因子：
17.1
作者：
Claesen J;Spagnolo JB;Ramos SF;Kurita KL;Byrd AL;Aksenov AA;Melnik AV;Wong WR;Wang S;Hernandez RD;Donia MS;Dorrestein PC;Kong HH;Segre JA;Linington RG;Fischbach MA;Lemon KP
通讯作者：
Lemon KP
DOI：
10.1073/pnas.2021683118
发表时间：
2021-05-25
影响因子：
11.1
作者：
Drott, Milton T.;Rush, Tomas A.;Keller, Nancy P.
通讯作者：
Keller, Nancy P.
影响因子：
5.7
作者：
Ghosh S;O'Connor TJ
通讯作者：
O'Connor TJ
影响因子：
16.6
作者：
Chevrette, Marc G.;Carlson, Caitlin M.;Currie, Cameron R.
通讯作者：
Currie, Cameron R.