A Droplet Microfluidics Based Platform for Mining Metagenomic Libraries for Natural Compounds

Area of Science:

• Microbiology
• Molecular Biology
• Bioengineering

Background:

• Environmental microbes are a source of novel bioactive compounds.
• Metagenomic libraries offer access to a wider range of compounds.
• Current methods limit the use of metagenomic libraries in mammalian cell applications.

Purpose of the Study:

• To develop an integrated platform for mining natural resources for pro-apoptotic compounds.
• To enable high-throughput screening of metagenomic libraries in mammalian cells.
• To overcome limitations of existing compound extraction and screening methods.

Main Methods:

• Utilized invasive Escherichia coli as a delivery vehicle for natural compounds.
• Employed droplet microfluidics for bacterial clone amplification and high-throughput screening.
• Developed a cell aggregate strategy to mitigate background apoptosis in assays.

Main Results:

• Demonstrated efficient delivery of natural compounds using modified E. coli.
• Successfully screened metagenomic libraries with mammalian cell assays without laborious extraction.
• Achieved high-throughput clonal screening and reduced background apoptosis.

Conclusions:

• The developed platform integrates bacterial delivery and droplet microfluidics for efficient mining of the metagenome.
• This approach facilitates the discovery of therapeutic compounds with potential applications in medicine.
• The platform provides a versatile tool for exploring natural resources for drug discovery.