A team of researchers from Manchester University, in the UK, developed a new method to produce antibiotics using gene editing techniques, according to a study published in Nature Communications. This procedure could pave the way for a new generation of antibiotics capable of fighting drug-resistant pathogens.
The idea is to use CRISPR-cas9 to alter certain enzymes present in bacteria —such as nonribosomal peptide synthetase (NPRS)—to produce clinically important antibiotics. These enzymes are involved in the synthesis of natural antibiotics, such as penicillin, but up until now, it’s been impossible to manipulate these enzymes to produce more effective antibiotics.
Antimicrobial resistance (AMR) is estimated to cause 700,000 fatalities every year. This number is expected to increase to 10 million by 2050, with an extra 28 million people forced into poverty unless the problem is contained.
The UK researchers believe CRISPR-cas9 could the the solution to produce better antibiotics and potentially lead to the development of new treatments to fight drug-resistant pathogens. “The emergence of antibiotic-resistant pathogens is one of the biggest threats we face today,” said Jason Micklefield, Professor of Chemical Biology at the Manchester Institute of Biotechnology, UK. “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.”
Many microorganisms in our environment have these enzymes that can produce compounds with very strong antibiotic activity. In fact, the most important antibiotics we use today came from these NRPS enzymes, including, for example, penicillin, vancomycin, and daptomycin.
Unfortunately, new pathogens are constantly emerging which are resistant to all of our existing antibiotics. In theory, one way to solve this issue would be to chemically create new antibiotics that can escape the resistance mechanisms in the pathogens. However, this is a complex and expensive method. Instead of creating something from scratch, the team from Manchester has perfected a way to use new gene editing tools to engineer already existing NPRS enzymes and “make” them produce new compounds. They hope this approach could also be applied to other enzymes, which are prolific sources of antibiotics and other therapeutic agents.
“We are now able to use gene editing to introduce targeted changes to complex NRPS enzymes, introducing alternative amino acids precursors into 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”, concluded Micklefield.
(1) Thong, W.L., Zhang, Y., Zhuo, Y. et al. Gene editing enables rapid engineering of complex antibiotic assembly lines. Nat Commun 12, 6872 (2021). https://doi.org/10.1038/s41467-021-27139-1