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Serratia marcescens Quinoprotein Glucose Dehydrogenase Activity Mediates Medium Acidification and Inhibition of Prodigiosin Production by Glucose

机译:粘质沙雷氏菌喹蛋白葡萄糖脱氢酶活性介导葡萄糖的中等酸化和对前黄素产生的抑制作用

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Serratia marcescens is a model organism for the study of secondary metabolites. The biologically active pigment prodigiosin (2-methyl-3-pentyl-6-methoxyprodiginine), like many other secondary metabolites, is inhibited by growth in glucose-rich medium. Whereas previous studies indicated that this inhibitory effect was pH dependent and did not require cyclic AMP (cAMP), there is no information on the genes involved in mediating this phenomenon. Here we used transposon mutagenesis to identify genes involved in the inhibition of prodigiosin by glucose. Multiple genetic loci involved in quinoprotein glucose dehydrogenase (GDH) activity were found to be required for glucose inhibition of prodigiosin production, including pyrroloquinoline quinone and ubiquinone biosynthetic genes. Upon assessing whether the enzymatic products of GDH activity were involved in the inhibitory effect, we observed that d-glucono-1,5-lactone and d-gluconic acid, but not d-gluconate, were able to inhibit prodigiosin production. These data support a model in which the oxidation of d-glucose by quinoprotein GDH initiates a reduction in pH that inhibits prodigiosin production through transcriptional control of the prodigiosin biosynthetic operon, providing new insight into the genetic pathways that control prodigiosin production. Strains generated in this report may be useful in large-scale production of secondary metabolites.
机译:粘质沙雷氏菌是用于研究次级代谢产物的模型生物。像许多其他次要代谢产物一样,具有生物活性的色素prodigiosin(2-甲基-3-戊基-6-甲氧基丙氨酸)也被富含葡萄糖的培养基所抑制。尽管先前的研究表明这种抑制作用是pH依赖性的,不需要环AMP(cAMP),但尚无有关介导这种现象的基因的信息。在这里,我们使用了转座子诱变来鉴定参与葡萄糖抑制prodigiosin的基因。已发现参与喹蛋白葡萄糖脱氢酶(GDH)活性的多个遗传基因座是抑制葡萄糖原菌素生产所需的,包括吡咯并喹啉醌和泛醌生物合成基因。通过评估GDH活性的酶产物是否与抑制作用有关,我们观察到d-葡萄糖酸1,5-内酯和d-葡萄糖酸,但不是d-葡萄糖酸,能够抑制prodigiosin的产生。这些数据支持了一个模型,其中喹蛋白GDH氧化d-葡萄糖引发了pH降低,从而通过对prodigiosin生物合成操纵子的转录控制而抑制了prodigiosin的产生,从而为控制prodigiosin产生的遗传途径提供了新的见识。本报告中产生的菌株可能在次级代谢产物的大规模生产中有用。

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