Omics Technologies to Understand Activation of a Biosynthetic Gene Cluster in Micromonospora sp. WMMB235: Deciphering Keyicin Biosynthesis
Omics Technologies to Understand Activation of a Biosynthetic Gene Cluster in Micromonospora sp. WMMB235: Deciphering Keyicin Biosynthesis
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DOI：
10.1021/acschembio.9b00223
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发表时间：
2019-06-01
影响因子：
4
通讯作者：
Bugni, Tim S.
中科院分区：
文献类型：
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作者：
Acharya, Deepa;Miller, Ian;Bugni, Tim S.
大量细菌基因组的DNA测序揭示了大量的孤儿生物合成基因簇（BGC），没有可识别的产物。对于那些真正沉默的孤儿簇，而不是那些其产物简单地逃避检测和簇相关性的孤簇，BGC沉默被假定是由这些簇在标准实验室条件下的转录失活引起的。在这里，我们采用了多组学的方法来证明如何种间相互作用调节keyicin生产kyc集群在转录组水平的共培养的kyc轴承小单孢菌属和红球菌属。我们进一步相关共培养依赖的keyicin生产的变化，在转录组和蛋白质组学的配置文件，并表明这些变化是由于小分子信号与群体感应途径一致。在将共培养中keyicin生产的各种因素拼凑在一起时，这项研究强调了组学技术如何加快未来理解和利用沉默BGC的努力。
DNA sequencing of a large collection of bacterial genomes reveals a wealth of orphan biosynthetic gene clusters (BGCs) with no identifiable products. BGC silencing, for those orphan clusters that are truly silent, rather than those whose products have simply evaded detection and cluster correlation, is postulated to result from transcriptional inactivation of these clusters under standard laboratory conditions. Here, we employ a multi-omics approach to demonstrate how interspecies interactions modulate the keyicin producing kyc cluster at the transcriptome level in cocultures of kyc-bearing Micromonospora sp. and a Rhodococcus sp. We further correlate coculture dependent changes in keyicin production to changes in transcriptomic and proteomic profiles and show that these changes are attributable to small molecule signaling consistent with a quorum sensing pathway. In piecing together the various elements underlying keyicin production in coculture, this study highlights how omics technologies can expedite future efforts to understand and exploit silent BGCs.