Insights into microbial cryptic gene activation and strain improvement: principle, application and technical aspects

Area of Science:

• Microbiology
• Biotechnology
• Metabolic Engineering

Background:

• Bacteria and fungi possess numerous silent secondary metabolite biosynthetic gene clusters.
• These cryptic pathways are often not expressed under standard laboratory conditions, limiting the discovery of novel compounds.

Purpose of the Study:

• To review current progress and methods for activating silent secondary metabolite biosynthetic pathways in microorganisms.
• To highlight genetic manipulation, elicitors, metabolism remodeling, and co-cultivation as key activation strategies.

Main Methods:

• Genetic manipulation of transcription and translation, specifically ribosome engineering.
• Utilization of elicitors to trigger gene expression.
• Metabolism remodeling and co-cultivation techniques.
• Detailed examination of S-adenosylmethionine's role in bacterial secondary metabolism.

Main Results:

• Successful activation of silent pathways leads to the discovery of novel secondary metabolites.
• Ribosome engineering offers precise control over gene expression.
• Metabolic engineering approaches can redirect cellular resources to activate pathways.

Conclusions:

• Activating silent gene clusters is a promising strategy for discovering new bioactive compounds.
• Understanding bacterial physiology, including the role of S-adenosylmethionine, is crucial for optimizing secondary metabolite production.