Dissecting the nitrogen regulation system of streptomycetes

链霉菌是无害的土壤细菌，是我们用于治疗传染病的绝大多数抗生素的主要来源，也为我们提供了许多其他药物，例如用于治疗癌症和帮助器官移植患者。这些化合物中的大多数被称为次级代谢物，因为它们的合成是缓慢的，并且通常发生在生长周期的后期。在细菌中，链霉菌也相对不寻常，因为它们具有复杂的生命周期，在此期间它们经历细胞形状和形式的许多变化，导致产生一系列坚固的孢子，这些孢子被分散，然后发芽重复循环。抗生素的产生和分化过程都只在一定的条件下发生，其中之一是氮源的可用性受到限制。在许多细菌中，让细胞决定是否缺乏氮的复杂控制过程已经很清楚，但到目前为止，我们还没有确切地确定这个过程在链霉菌中是如何工作的。我们计划结合我们对其他细菌中“氮控制”过程的了解，以及链霉菌中存在的所有基因的最新信息，开始剖析这些具有重要经济意义的细菌中构成氮控制系统的传感器和开关。如果我们能做到这一点，它将提供重要的信息，使我们能够操纵这些细菌，以控制它们何时开始合成抗生素等重要化合物，以及产生的数量。

Streptomycetes are harmless soil bacteria that are the primary source of the vast majority of antibiotics that we use to cure infectious disease, as well as providing us with numerous other medicines that are used, for example, to treat cancer and to help organ transplant patients. Most of these compounds are called secondary metabolites, in that their synthesis is dispensable and often occurs late in the growth cycle. Amongst the bacteria, streptomycetes are also relatively unusual in that they have a complex life cycle during which they undergo a number of changes in cell shape and form leading to the production of a chain of robust spores that are dispersed and then germinate to repeat the cycle. Both the production of antibiotics and the differentiation process occur only under certain conditions, one of which is a limitation on the availability of nitrogen sources. In many bacteria the complex control processes that allow the cell to determine whether it is short of nitrogen are well understood, but up until now we have not determined exactly how this process works in streptomycetes. We plan to use a combination of our knowledge of how this process of 'nitrogen control' works in other bacteria, together with recent information on all the genes that are present in streptomycetes, to begin to dissect the sensors and switches that make up the nitrogen control system in these economically important bacteria. If we can achieve this, it will provide important information that will allow us to manipulate these bacteria to control when they begin to synthesise important compounds such as antibiotics, and the amounts produced.