Department of Cell Biology and Molecular Genetics, The University of Maryland, 3112 Biosciences Research Building, College Park, Maryland 20742, USA.
Department of Biochemistry and Biophysics, Texas A&M University, TAMU 2128 - Rm 435, College Station, Texas 77843, USA.
Nat Microbiol. 2017 Feb 13;2:17003. doi: 10.1038/nmicrobiol.2017.3.
A valuable resource available in the search for new natural products is the diverse microbial life that spans the planet. A large subset of these microorganisms synthesize complex specialized metabolites exhibiting biomedically important activities. A limiting step to the characterization of these compounds is an elucidation of the genetic regulatory mechanisms that oversee their production. Although proteins that control transcription initiation of specialized metabolite gene clusters have been identified, those affecting transcription elongation have not been broadly investigated. In this study, we analysed the phylogenetic distribution of the large, widespread NusG family of transcription elongation proteins and found that it includes a cohesive outgroup of paralogues (herein coined LoaP), which are often positioned adjacent or within gene clusters for specialized metabolites. We established Bacillus amyloliquefaciens LoaP as a paradigm for this protein subgroup and showed that it regulated the transcriptional readthrough of termination sites located within two different antibiotic biosynthesis operons. Both of these antibiotics have been implicated in plant-protective activities, demonstrating that LoaP controls an important regulon of specialized metabolite genes for this microorganism. These data therefore reveal transcription elongation as a point of regulatory control for specialized metabolite pathways and introduce a subgroup of NusG proteins for this purpose.
在寻找新的天然产物时，一种有价值的资源是遍布全球的多样化微生物生命。这些微生物中有很大一部分合成具有生物医学重要活性的复杂特殊代谢物。这些化合物的特征在于阐明负责其生产的遗传调控机制。虽然已经鉴定出控制特殊代谢物基因簇转录起始的蛋白质，但那些影响转录延伸的蛋白质尚未广泛研究。在这项研究中，我们分析了广泛存在的转录延伸蛋白 NusG 家族的系统发育分布，发现它包括一个凝聚力的旁系群（在此称为 LoaP），它们通常位于特殊代谢物基因簇的相邻或内部。我们确定了解淀粉芽胞杆菌的 LoaP 作为该蛋白亚群的范例，并表明它调节了位于两个不同抗生素生物合成操纵子内的终止位点的转录通读。这两种抗生素都与植物保护活性有关，这表明 LoaP 控制了该微生物特殊代谢物基因的重要调控基因。因此，这些数据揭示了转录延伸是特殊代谢物途径的调控控制点，并为此引入了一类 NusG 蛋白。
