Heat Shock Repressor HspR Directly Controls Avermectin Production, Morphological Development, and H₂O₂ Stress...

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• The heat shock response (HSR) is crucial for cellular survival under thermal stress.
• In Streptomyces, a major antibiotic producer, HSR is primarily regulated by repressors like HspR.
• The broader regulatory roles of HspR beyond HSR were previously unknown.

Purpose of the Study:

• To elucidate the pleiotropic functions of HspR in Streptomyces avermitilis.
• To investigate HspR's role in avermectin production, morphological development, and stress responses.
• To identify HspR-regulated genes and understand its interaction with other regulators like PhoP.

Main Methods:

• Gene expression analysis (activation and repression) of HspR targets.
• Identification of HspR-binding sites using sequence analysis.
• Investigating protein-protein interactions between HspR and PhoP.
• Assessing the impact of HspR overexpression on avermectin production.

Main Results:

• HspR pleiotropically regulates avermectin biosynthesis, development, and H2O2 stress response genes.
• HspR functions as a dual transcriptional activator (for avermectin and H2O2 genes) and repressor (for heat shock and developmental genes).
• HspR interacts with PhoP to coregulate heat shock genes, with PhoP also controlling distinct heat shock genes.
• Overexpression of HspR significantly enhanced avermectin production in Streptomyces avermitilis.

Conclusions:

• HspR is a key regulator coordinating diverse biological processes in Streptomyces, including antibiotic production and stress adaptation.
• HspR exhibits a novel dual activator/repressor function, expanding the known roles of MerR-family regulators.
• PhoP plays a significant role in HSR regulation, interacting with HspR and controlling its own set of target genes.
• HspR manipulation offers a promising strategy for enhancing antibiotic yields in industrial Streptomyces strains.