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

链霉菌次生代谢启动和形态发育调控系统的综合研究

基本信息

批准号：
13854005
负责人：
HORINOUCHI Sueharu
金额：
$ 77.63万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (S)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2005
项目状态：
已结题

项目摘要

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.

1.遗传和生物学方法已经揭示了A因子调节级联的整体情况。例如，信号从A因子转移到链霉菌素生物合成基因始于AFSA，该基因从甘油衍生物和β-酮酸中催化A因子的生物合成。一旦A因子的细胞内浓度达到临界水平，其信息就会将其转移到ARPA（A-Factor受体和转录阻遏物）向ADPA（转录激活剂）到STRR（途径特异性转录激活剂的链霉菌素生物合成）到链霉菌生物合成的基因。此外，ARPA的X射线晶体学揭示了A因子如何将ARPA与DNA分离。链霉菌（一种边界微生物）对二次代谢和形态发展的荷尔蒙调节的详细研究对微生物学产生了重大影响。这项研究也可用于通过使用DNA微阵列技术对A因子调节级联的进一步详细和全面分析。2.a转录激活剂AFSR通过丝氨酸/苏氨酸激酶AFSK在其苏氨酸住所（S）上磷酸化。 AFSK通过在THR-168上的自磷酸化来自动激活其激酶活性。磷酸化的AFSR激活AFS的启动子，其基因产物以某种未知的方式增强了次级代谢。涉及AFSK/AFSR/AFSS的调节系统是细菌世界中最广泛研究的系统。3。葡萄糖抑制葡萄糖是链霉菌中继发代谢和形态发生的另一种调节系统。分离了几种以高浓度的葡萄糖产生抗生素和孢子的突变体，我认为这将是研究分解代谢产物抑制作用的良好材料。此外，还发现cAMP和钙调蛋白样蛋白可以控制链霉菌的形态发生。这些调节系统将通过DNA微阵列进行研究。