Finding new pathway-specific regulators by clustering method using threshold standard deviation based on DNA chip data of Streptomyces coelicolor

Abstract

In order to identify the regulators involved in antibiotic production or time-specific cellular events, the messenger ribonucleic acid (mRNA) expression data of the two gene clusters, actinorhodin (ACT) and undecylprodigiosin (RED) biosynthetic genes, were clustered with known mRNA expression data of regulators from S. coelicolor using a filtering method based on standard deviation and clustering analysis. The result identified five regulators including two well-known regulators namely, SCO3579 (WlbA) and SCO6722 (SsgD). Using overexpression and deletion of the regulator genes, we were able to identify two regulators, i.e., SCO0608 and SCO6808, playing roles as repressors in antibiotics production and sporulation. This approach can be easily applied to mapping out new regulators related to any interesting target gene clusters showing characteristic expression patterns. The result can also be used to provide insightful information on the selection rules among a large number of regulators.

The TetR Family of Regulators

“…Our analysis of TFRs from members of the genus Streptomyces, the majority of which encode over 100 TFRs, reveals five TFRs that are conserved in all of the close to 70 strains sequenced as of 26 April 2013, with another seven TFRs highly conserved and missing in only one strain. One of these TFRs is more broadly conserved in Actinobacteria, while another two have been implicated in the regulation of antibiotic production in members of the genus (6,35). We surmise that all 10 of these TFRs play an important role in regulating general processes important to antibiotic production and development in Streptomyces, while less conserved TFRs are more likely to play a role in regulating specific adaptive functions such as the catabolism of a specific carbon source or resistance to a specific antibiotic.…”

An integrative approach for high-throughput screening and characterization of transcriptional regulators in Streptomyces coelicolor

“…Based on the results, the deletion mutants of these candidate regulators were constructed, and their potential functions in antibiotic production are currently being investigated. Although the detailed characterizations of these regulators are not yet completed, they seem to affect the ACT and RED biosynthesis [16,17], suggesting that the optimized rapid screening method is quite efficient and useful to understand the antibiotic production-associated transcriptional networks in Streptomyces. Table 1 DACA results using the promoter regions of actII-ORF4 and redD from S. coelicolor (modified from [16]).…”

“…SCO6722 (SsgD) known to be involved in the synthesis of peptidoglycan along the lateral cell wall synthesis and sporulation might also contribute to antibiotic production [26]. Regarding the other three candidate regulators (SCO1699, SCO0608, and SCO6808), we characterized their potential functions as repressors in antibiotic production by constructing individual overexpression and deletion mutants [17]. It is known that the genes whose products are necessary only for specific period of time during the growth usually act as repressor regulators [27].…”

Comparative study of three commonly used continuous deterministic methods for modeling gene regulation networks

“…However, the relationships between co-regulated genes are very complex [30] and it is important to identify the key genes that act as regulators to the clusters of co-expressed genes [31]. Once the gene regulators are identified they may be used to construct simplified network models that are useful for reverse-engineering [32].…”