RNA Degradation and Antibiotic Synthesis in Streptomyces

Emory University, Atlanta GA

Investigators

Abstract

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.