Comprehensive study on regulatory systems for the initiation of secondary metabolism and morphological development in Streptomyces

1.遗传和生物学方法揭示了A因子调控级联反应的整体图景。例如，从A因子到链霉素生物合成基因的信号转导始于AFSA，它催化从甘油衍生物和β-酮酸生物合成A因子。一旦细胞内A因子浓度达到临界水平，其信息就被传递到ARPA(A因子受体和转录抑制因子)、AdpA(转录激活因子)和STRR(链霉素生物合成途径特异性转录激活因子)，传递到链霉素生物合成基因。此外，ARPA的X射线结晶学揭示了A因子是如何将ARPA与DNA解离的。链霉菌作为一种边界微生物，对其次生代谢和形态发育的激素调控进行了详细的研究，对微生物学产生了重大影响。本研究也有助于利用基因芯片技术进一步详细和全面地分析A因子调控级联反应。2.转录激活因子AfsR在其苏氨酸残基(S)上被丝氨酸/苏氨酸激酶AfsK磷酸化。AfsK通过苏氨酸转运蛋白-168上的自动磷酸化来自我激活其激酶活性。AFsR的磷酸化激活AFSS的启动子，AFSS的基因产物以某种未知的方式增强次生代谢。涉及AfsK/AfsR/AFSS的调控系统是细菌界研究最广泛的系统。3.葡萄糖抑制分解代谢是链霉菌次生代谢和形态发生的另一个调控系统。分离到了几个在高浓度葡萄糖中产生抗生素和孢子的突变株，我相信这将是研究分解代谢抑制的很好材料。此外，cAMP和类钙调素蛋白也控制着链霉菌的形态发生。这些调控系统将通过DNA微阵列进行研究。

1.The overall picture of the A-factor regulatory cascade has been revealed by genetic and biological approaches. For example, the signal transduction from A-factor to the streptomycin biosynthesis genes starts with AfsA that catalyzes the biosynthesis of A-factor from a glycerol derivative and a β-keto acid. Once the intracellular concentration of A-factor reaches a critical level, its information is transferred to ArpA (A-factor receptor and transcriptional repressor) to AdpA (transcriptional activator) to StrR (pathway-specific transcriptional activator for streptomycin biosynthesis) to the streptomycin biosynthesis genes. In addition, X-ray crystallography of ArpA revealed how A-factor dissociates ArpA from the DNA. The detailed study of the hormonal regulation of secondary metabolism and morphological development in Streptomyces, a boundary microorganisms, has given a big impact on microbiology. This study is also useful for further detailed and comprehensive analysis of the A-factor regulatory cascade by using DNA microarray techniques.2.A transcriptional activator AfsR is phosphorylated on its threonine residue(s) by a serine/threonine kinase AfsK. AfsK self-activates its kinase activity by autophosphorylation on Thr-168. The phosphorylated AfsR activates the promoter of afsS, the gene product of which enhances secondary metabolism in some unknown way. The regulatory system involving AfsK/AfsR/AfsS is the most extensively studied system in the bacterial world.3.Catabolite repression by glucose is another regulatory system for secondary metabolism and morphogenesis in Streptomyces. Several mutants that produce antibiotics and spores in a high concentration of glucose were isolated, which I believe will be good material to study catabolite repression. In addition, cAMP and calmodulin-like protein were also found to control morphogenesis of Streptomyces. These regulatory systems will be studied by means of DNA microarray.