Bacteria can transfer genetic material with each other. This ability not only contributes to the spread of antibiotic resistance but also allows them to adapt to new environments.
Scientists from the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) and the German Center for Infection Research (DZIF) have developed a pioneering technique to take advantage of this ability and unlock the potential to revolutionize drug discovery.
The team utilized an innovative approach called ACTIMOT (Advanced Cas9-mediaTed In vivo MObilization and mulTiplication of BGCs), which uses CRISPR-Cas9 gene-editing technology to extract and amplify biosynthetic gene clusters (BGCs) from bacteria.
These BGCs, often dormant under lab conditions, contain genetic blueprints for bioactive natural products. ACTIMOT liberates these clusters by inserting them into plasmids or mobile genetic units that replicate within bacterial cells. During this process, new compounds are often produced. Otherwise, the plasmids can be transferred to alternative strains better suited for production.
Chengzhang Fu, a junior research group leader at HIPS, said:
“Many biosynthetic gene clusters remain suppressed under laboratory conditions for various reasons. Our approach mimics natural bacterial processes to amplify these clusters directly in the cell, providing access to previously hidden natural products.”
A recent study has shown that ACTIMOT determined 39 new natural products from four previously unknown natural product classes. The team initially applied the method to Streptomyces bacteria and plans to expand it to other species with high biosynthetic potential.
Moreover, ACTIMOT could drive large-scale production of valuable natural products, map unknown genetic pathways, and facilitate the optimization of natural compounds. These developments could significantly expand the resources available for creating promising pharmaceuticals.
Read the full article here to learn more about the innovative genetic method designed to produce new active ingredients in bacteria.
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