Changing Biosynthetic Profiles by Expressing bldA in Streptomyces Strains

Area of Science:

• Microbiology
• Natural Product Discovery
• Molecular Biology

Background:

• Streptomyces calvus exhibits a bald phenotype due to a cryptic gene cluster.
• The bldA gene was previously identified as crucial for restoring sporulation in S. calvus.
• This gene also influences the production of secondary metabolites.

Purpose of the Study:

• To investigate the effect of expressing the bldA gene in various poorly sporulating Streptomyces strains.
• To identify novel natural products or enhanced production of known compounds in these strains.
• To explore the broader role of bldA in Streptomyces secondary metabolism.

Main Methods:

• Expression of the bldA gene in 15 different poorly sporulating Streptomyces strains.
• High-Performance Liquid Chromatography (HPLC) profiling to detect and compare metabolite production.
• Isolation and structure determination of newly produced compounds.

Main Results:

• Expression of bldA resulted in the production of new compounds in 7 out of 15 strains.
• Two strains showed overproduction of known compounds after bldA expression.
• Two novel compounds were successfully isolated and their chemical structures elucidated.
• Restored sporulation was observed in responsive strains.

Conclusions:

• The bldA gene plays a significant role in activating cryptic gene clusters for natural product biosynthesis across diverse Streptomyces species.
• Targeted expression of bldA is a viable strategy for discovering novel secondary metabolites.
• Understanding bldA's function can aid in engineering Streptomyces for enhanced natural product yields.