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The bacterium Streptomyces roseosporus is the source of many common antibiotics such as daptomycin, which is active against methicillin-resistant Staphylococcus aureus (MRSA) and glycopeptide-resistant enterococci. A*STAR researchers have just unearthed a new antibiotic, auroramycin, from a silent biosynthetic gene cluster discovered in the S. roseosporus genome, and believe there are many more just waiting to be found.
"This strain of bacteria is very well studied. It's interesting that, even after so many molecules have been discovered, we now have a new antibiotic simply because we have the tools to access it," explains Yee Hwee Lim of the A*STAR Institute of Chemical and Engineering Sciences and Fong Tian Wong of the A*STAR Molecular Engineering Lab. Lim, Wong and colleagues used CRISPR-Cas9 to introduce a potent gene transcription activator—the kasO* promoter—into the bacterial genome to activate expression of an entire cryptic biosynthetic gene cluster. The gene cluster was found to encode auroramycin, an antibiotic with potent antibacterial activity against Gram-positive bacteria, including MRSA and vancomycin-resistant Enterococcus faecalis (VRE).
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"Initially, we didn't know what kind of molecule we were getting. It took a while for us to figure out what we were working with," describes Lim and Wong. The cluster was predicted to encode a type I polyketide synthase but, due to the high guanine-cytosine content and repetitive sequences within...
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