The art and design of functional metagenomic screens

This article summarizes general design principles for functional metagenomics. The focus is on Escherichia coli as an expression host, although alternative host–vector systems are discussed in relation to optimizing gene recovery in activity-based screens. Examples of DNA isolation and enrichment approaches, library construction and phenotypic read-out are described with special emphasis on the use of high throughput technologies for rapid isolation of environmental clones encoding phenotypic traits of interest.

► We describe the power and limitations of functional metagenomic screens.
► We emphasize design principles and compare host-vector systems.
► Examples of successful screens using E. coli host strains are highlighted.
► Microfluidic approaches for extending screening throughput are discussed.