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Functional metagenomic studies enable scientists to discover novel genes that encode biologically active molecules.
These assays include top agar overlay assays where antibiotics generate zones of growth inhibition against test microbes, and pH assays that can screen for pH change due to newly synthesized molecules using pH indicator on an agar plate.
Substrate-induced gene expression screening ( SIGEX ), a method to screen for the expression of genes that are induced by chemical compounds, has also been used to search genes with specific functions.
These led to the discovery and isolation of several novel proteins and small molecules.
For example, the Schipper group identified three eDNA derived AHL lactonases that inhibit biofilm formation of Pseudomonas aeruginosa via functional metagenomic assays.
However, these functional screening methods require a good design of probes that detect molecules being synthesized and depend on the ability to express metagenomes in a host organism system.

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