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Unmuting large silent genes lets bacteria produce new molecules, potential drug candidates

By enticing away the repressors dampening unexpressed, silent genes in Streptomyces bacteria, researchers at the University of Illinois have unlocked several large gene clusters for new natural products, according to a study [DOI: 10.1038/s41589-018-0187-0] [DX] published in the journal Nature Chemical Biology.

[...] The researchers previously demonstrated a technique to activate small silent gene clusters using CRISPR technology. However, large silent gene clusters have remained difficult to unmute. Those larger genes are of great interest to [study leader Huimin] Zhao's group, since a number of them have sequences similar to regions that code for existing classes of antibiotics, such as tetracycline.

To unlock the large gene clusters of greatest interest, Zhao's group created clones of the DNA fragments they wanted to express and injected them into the bacteria in hopes of luring away the repressor molecules that were preventing gene expression. They called these clones transcription factor decoys.

[...] Of the eight new molecules produced, the researchers purified and determined the structure of two molecules, and described one in detail in the study – a novel type of oxazole, a class of molecules often used in drugs.

Original Submission