Wallace K K, Payne G F, Speedie M K
Department of Chemical and Biochemical Engineering, University of Maryland, Baltimore.
J Ind Microbiol. 1990 Sep;6(1):43-8. doi: 10.1007/BF01576175.
A defined medium containing glucose and ammonium as the sole carbon and nitrogen sources was developed to support growth and streptonigrin production. In this defined medium, increased initial levels of ammonium resulted in increased growth suggesting that nitrogen is the growth limiting nutrient. In some cases, increased initial ammonium levels resulted in decreased specific streptonigrin productivity, suggesting that nitrogen regulatory mechanisms may adversely affect streptonigrin biosynthesis. This suggestion that nitrogen regulation adversely affects antibiotic biosynthesis is further supported by results from two studies in which the ammonium supply to the cells was controlled. In the first study, streptonigrin productivity and final titer were enhanced by the addition of an ammonium trapping agent. In the second experiment, when ammonium chloride was fed slowly throughout the course of cultivation, the production phase was lengthened and the maximum antibiotic concentration was enhanced compared to the batch controls containing either the same initial or the same total ammonium chloride levels. Although our results indicate streptonigrin production may be subject to nitrogen regulatory mechanisms, the effect of nitrogen on streptonigrin production cannot be strictly correlated to the extracellular ammonium concentration. In fact, we observed that when ammonium was depleted from the medium, streptonigrin production ceased.
开发了一种以葡萄糖和铵作为唯一碳源和氮源的限定培养基，以支持生长和链黑菌素的产生。在这种限定培养基中，铵的初始水平增加导致生长增加，这表明氮是生长限制营养素。在某些情况下，铵的初始水平增加导致链黑菌素的比生产率下降，这表明氮调节机制可能会对链黑菌素生物合成产生不利影响。两项控制细胞铵供应的研究结果进一步支持了氮调节对抗生素生物合成产生不利影响这一观点。在第一项研究中，添加铵捕获剂提高了链黑菌素的生产率和最终效价。在第二项实验中，与含有相同初始氯化铵水平或相同总氯化铵水平的分批对照相比，在整个培养过程中缓慢添加氯化铵时，生产阶段延长，最大抗生素浓度提高。尽管我们的结果表明链黑菌素的产生可能受氮调节机制的影响，但氮对链黑菌素产生的影响不能严格与细胞外铵浓度相关联。事实上，我们观察到当培养基中的铵耗尽时，链黑菌素的产生就会停止。
