“This is an exciting advance in efforts to replenish the antibiotic arsenal,” Steven Rutherford, a microbial science expert at Genentech, wrote in a commentary article in Nature. “More broadly, the study provides a road map showing how genome mining can be used to identify new antibacterial natural products and strategies for their use.”
The way megacluster products attack is by making biotin, also known as vitamin B7. This nutrient is essential for growth and virulence in many human pathogens, and, more specifically, it is a cofactor that critical metabolic enzymes require to function properly. Some bacteria can remove biotin from their surroundings, but this is generally rare, and bacteria have evolutionarily conserved pathways to make it themselves.
Brown and colleagues interestingly found biotin-targeted megaclusters. Streptomyces Species that have been very well studied. Streptomyces These are bacteria that live in the soil and are known as a gold mine for the discovery of antibiotic molecules. Many natural products have already been extracted from them, including the antibiotic streptomycin, an essential drug discovered in the 1940s. Despite this, megaclusters have been overlooked until now, possibly partly because bacteria in laboratories are often grown in nutrient-rich media.
fresh strategy
Additionally, when researchers are looking for new antibiotics in bacterial genomes, they scan biosynthetic gene clusters (BGCs) that may be responsible for the production of single molecules. But Brown’s team identified a cluster of four — a megacluster — that produces not just one, but four molecules that work in different ways to travel along the biotin pathway. Careful study has shown that three groups produce antibiotic molecules – stravidin, acidomycin, dapomycin – that each thwart a different enzyme in the biotin biosynthesis pathway. The remaining fourth cluster produces 2-methyl-7-keto-8-aminopelargonic acid, or α-Me-KAPA, which appears to be a dummy molecule that replaces the biotin precursor, basically hijacking the pathway to yield a useless biotin-like compound.
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