UK scientists have used genetic methods to control the chemical structures of pacidamycin antibiotics produced in bacteria. Their approach allows them to ‘dial into’ particular molecules, and to generate new pacidamycins.
The pacidamycins are uridyl peptide antibiotics with specific activity against Pseudomonas aeruginosa, a common cause of hospital infections. They target a protein in the bug’s cell wall. Around 20 pacidamycins are produced naturally by Streptomyces coeruleorubidus, although they have never been used clinically.
As with many natural products, purifying one from a suite of similar compounds can be tricky. But Rebecca Goss and colleagues at the University of East Anglia say their approach allows them to steer production in the direction they choose. ‘We’ve been able to introduce the genes into an organism that doesn’t naturally produce pacidamycin and rather than it making a whole forest of different peaks – of different antibiotics – which would be a separation nightmare, we’ve been able to bolt in the genes to make the different members of the family,’ explains Goss. ‘So we’ve been able to “dial a molecule” within the bug.’