Scientists have used gene-editing advances to achieve a ten-fold increase in the production of super-bug-targeting formicamycin antibiotics. The John Innes Centre (UK) researchers used the technology to create a new strain of Streptomyces formicae bacteria which over-produces the medically promising molecules. The results were reported in an article published on January 12, 2021 in Cell Chemical Biology. The open-access article is titled “Re-Wiring the Regulation of the Formicamycin Biosynthetic Gene Cluster to Enable the Development of Promising Antibacterial Compounds.” Discovered within the last ten years, formicamycins have great potential because, under laboratory conditions, superbugs like methicillin-resistant Staphylococcus aureus (MRSA) do not become resistant to them. However, Streptomyces formicae only produce the antibiotics in small quantities. This has made it difficult to scale up purification for further study and is an obstacle to the molecules being taken forward for clinical trials. In a new study, researchers used CRISPR/Cas9 genome editing to make an S. formicae strain which produces ten times more formicamycins on agar plates and even more in liquid cultures. Using DNA sequencing the researchers found that the formicamycin biosynthetic gene cluster consists of 24 genes and is controlled by the activity of three key regulators inside the cluster. The scientists used CRISPR/Cas9 to make changes in regulatory genes and measured how much of the antibiotics were produced. CRISPR/Cas9 involves using part of a microbial immune system to make targeted changes in DNA. Through uncovering the roles of the three important regulators, the team was able to combine mutations to maximise production.
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