New research has been published in Nature Communications, describing how a team of scientists from the University of Manchester used gene editing to manufacture new antibiotics.
The team used CRISPR-Cas9 gene editing to create new non-ribosomal peptide synthetase (NRPS) enzymes, critical in the natural production of antibiotics like penicillin. Previously, manipulating these enzymes to create more potent antibiotics that are less susceptible to growing microbial antibiotic resistance has been a challenge.
The UK government has estimated that antimicrobial resistance (AMR) will lead to 700,000 deaths each year globally and predict this will climb to 10 million by 2050, costing the global economy ~$100 trillion.
"The emergence of antibiotic-resistant pathogens is one of the biggest threats we face today. The gene-editing approach we developed is a very efficient and rapid way to engineer complex assembly line enzymes that can produce new antibiotic structures with potentially improved properties," said Jason Micklefield, Professor of Chemical Biology at the Manchester Institute of Biotechnology (MIB).
Instead of struggling to produce entirely new antibiotics from scratch to combat new emerging pathogens for which currently existing antibiotics are relatively ineffective, gene editing allowed the team to use the natural mechanisms in place for antibiotic production to their advantage. Editing the NRPS enzymes permitted them to build antibiotics with different amino acids in their sequence, ultimately producing new antibiotics.
"We are now able to use gene editing to introduce targeted changes to complex NRPS enzymes, enabling alternative amino acids precursors to be incorporated into the peptide structures. We are optimistic that our new approach could lead to new ways of making improved antibiotics which are urgently needed to combat emerging drug-resistant pathogens," said Micklefield.
You can read more from the study here.