Stella Nicholas A, Fender James E, Lahr Roni M, Kalivoda Eric J, Shanks Robert M Q
Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, USA.
Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, USA ; College of Medicine, University of Vermont, Burlington, USA.
Adv Microbiol. 2012 Dec 1;2(4). doi: 10.4236/aim.2012.24065.
Generation of many useful microbe-derived secondary metabolites, including the red pigment prodigiosin of the bacterium , is inhibited by glucose. In a previous report, a genetic approach was used to determine that glucose dehydrogenase activity (GDH) is required for inhibiting prodigiosin production and transcription of the prodigiosin biosynthetic operon (). However, the transcription factor(s) that regulate this process were not characterized. Here we tested the hypothesis that HexS, a LysR-family transcription factor similar to LrhA of , is required for inhibition of prodigiosin by growth in glucose. We observed that mutation of the gene in allowed the precocious production of prodigiosin in glucose-rich medium conditions that completely inhibited prodigiosin production by the wild type. Unlike previously described mutants able to generate prodigiosin in glucose-rich medium, mutants exhibited GDH activity and medium acidification similar to the wild type. Glucose inhibittion of expression was shown to be dependent upon HexS, suggesting that HexS is a key transcription factor in secondary metabolite regulation in response to medium pH. These data give insight into the prodigiosin regulatory pathway and could be used to enhance the production of secondary metabolites.
包括细菌红色色素灵菌红素在内的许多有用的微生物衍生次级代谢产物的生成会受到葡萄糖的抑制。在之前的一份报告中，采用了一种遗传学方法来确定葡萄糖脱氢酶活性（GDH）是抑制灵菌红素生成以及灵菌红素生物合成操纵子转录所必需的。然而，调节这一过程的转录因子尚未得到鉴定。在此，我们检验了这样一个假设：HexS，一种与[具体细菌名称]的LrhA相似的LysR家族转录因子，是葡萄糖生长条件下抑制灵菌红素生成所必需的。我们观察到，[具体细菌名称]中hexS基因的突变使得在富含葡萄糖培养基条件下能早熟产生灵菌红素，而这种条件会完全抑制野生型的灵菌红素生成。与之前描述的能够在富含葡萄糖培养基中产生灵菌红素的突变体不同，[具体细菌名称]突变体表现出与野生型相似的GDH活性和培养基酸化现象。葡萄糖对[具体细菌名称]表达的抑制作用被证明依赖于HexS，这表明HexS是响应培养基pH值的次级代谢产物调控中的关键转录因子。这些数据为灵菌红素调控途径提供了深入了解，可用于提高次级代谢产物的产量。
