RNA Degradation and Antibiotic Synthesis in Streptomyces

链霉菌是革兰氏阳性土壤细菌，以其形成被称为孢子(孢子形成)的休眠细胞的能力以及生产世界各地临床和兽医中使用的大多数抗生素而闻名。链霉菌属的成员生产常见的抗生素，如链霉素、氨苄西林和四环素作为天然产物。近年来，关于链霉菌产生抗生素的调控机制，已经获得了大量的信息。尚未详细研究的一种可能的监管水平与遗传信息的稳定性有关。在其他生物体中，已知调节遗传信息的稳定性可以控制基因的功能。有人建议研究遗传信息稳定性在天蓝色链霉菌抗生素生产调控中的作用。天蓝色假单胞菌产生四种抗生素，其中放线菌素(ACT)和十一烷基灵芝菌素(RED)将在本研究中进行检测。研究的具体目的如下。(1)已知参与决定细菌系统中遗传信息稳定性的两种酶的基因将被克隆。(2)将研究这些克隆基因的表达(即基因产物的产生)对ACT和RED产生所需的两种蛋白质遗传信息稳定性的影响。(3)决定信息稳定性的基因的表达对ACT和红色抗生素的产生的影响将被确定。如果检测到这种影响，将评估这些影响与抗生素生产所需遗传信息稳定性的关系。(4)利用基因工程技术，试图人为地提高ACT和红色产生的调节分子的遗传信息的稳定性。增加相关遗传信息的稳定性可能会导致抗生素产量的增加，而抗生素的合成受这些信息编码的蛋白质的调节。因此，有可能通过稳定抗生素生产所需的关键基因的遗传信息来增加抗生素产量。因此，拟议的研究很可能对抗生素的生产产生重大影响。(5)在以前的研究中，已经确定了一种名为abbB的基因，它控制着天蓝色葡萄球菌通常产生的所有四种抗生素的产生。该基因编码一种蛋白质，影响细菌中遗传信息的稳定性。将尝试确定受abbB影响的基因，并进一步评估信息稳定性影响抗生素生产的分子机制。

Streptomyces, Gram-positive soil bacteria, are notable for their ability to form dormant cells called spores (sporulation) and production of most of the antibiotics used worldwide in clinical and veterinary medicine. Members of the genus Streptomyces produce common antibiotics such as streptomycin, ampicillin and tetracycline as natural products. A considerable amount of information has been obtained in recent years regarding the mechanisms that regulate the production of antibiotics by Streptomyces. One possible level of regulation that has not been studied in detail concerns the stability of the genetic message. In other organisms, it is known that modulating the stability of the genetic message can control the function of genes. It is proposed to examine the role of genetic message stability in the regulation of antibiotic production by Streptomyces coelicolor. S. coelicolor produces four antibiotics, two of which, actinorhodin (act) and undecylprodigiosin (red) will be examined in this study. Specific aims of the research are as follows. (1) The genes for two enzymes known to be involved in determining the stability of the genetic message in bacterial systems will be cloned. (2) The effects of the expression of those cloned genes (i.e., the production of the gene products) on the stability of the genetic message for two proteins known to be required for act and red production will be studied. (3) The effects of the expression of the genes that determine message stability on the production of the act and red antibiotics will be determined. If such effects are detected, the relationship of those effects to the stability of genetic messages required for antibiotic production will be assessed. (4) Using genetic engineering techniques, attempts will be made to artificially increase the stability of the genetic messages for the regulators of act and red production. It is possible that increasing the stability of the genetic messages in question will lead to increased production of the antibiotics whose synthesis is regulated by the proteins encoded by those messages. It may thus be possible to increase antibiotic yields by stabilizing the genetic messages for key genes required for antibiotic production. Thus, the proposed studies may well have significant implications for the production of antibiotics. (5) In previous studies, a gene designated absB has been identified that controls production of all four of the antibiotics normally produced by S. coelicolor. That gene encodes a protein that affects the stability of the genetic message in bacteria. Attempts will be made to identify the genes that are in turn affected by absB and to assess further the molecular mechanism by which message stability affects antibiotic production.