Scientists have discovered a new avenue to produce complex antibiotics that exploits gene editing to reprogram urgently needed future drug pathways to combat antimicrobial resistance, treat neglected diseases and treat future epidemics.
Researchers from the University of Manchester have discovered a new way to manipulate key assembly line enzymes in bacteria that could pave the way for a new generation of antibiotic treatments.
New research published today in Nature Communications, describes how CRISPR-Cas9 gene editing can be used to create new non-chromosomal peptide (NRPS) enzymes that deliver clinically important antibiotics. NRPS enzymes are prolific producers of natural antibiotics such as penicillin. However, until now, manipulating these complex enzymes to produce new and more effective antibiotics has been a major challenge.
The UK government suggests that antimicrobial resistance (AMR) infections are expected to cause 700,000 deaths each year globally and are expected to rise to 10 million, costing the global economy $100 trillion by 2050. Antimicrobial resistance also threatens many United Nations Sustainable Development Goals (SDGs), with an additional 28 million people who could be forced to join extreme poverty by 2050 unless antimicrobial resistance is contained.
The Manchester team says the gene-editing process could be used to produce improved antibiotics and may lead to the development of new therapies to help fight the disease. Drug-resistant pathogens and diseases in the future. “The emergence of antibiotic-resistant pathogens is one of the biggest threats we face today,” explains Jason Micklefield, Professor of Chemical Biology at Manchester Institute of Biotechnology (MIB), UK.
“The gene-editing method we have developed is a very efficient and rapid way to engineer complex assembly line enzymes that can produce new antibiotic formulations with potentially improved properties.”
Microorganisms in our environment, such as soil-dwelling bacteria, have developed non-chromosomal peptide synthesis (NRPS) enzymes that assemble building blocks named Amino acids In peptide products that often have very strong antibiotic activity. Many of the most therapeutically important antibiotics, used in clinic today, are derived from NRPS enzymes (eg penicillin, vancomycin and daptomycin).
Unfortunately, deadly pathogens that are resistant to all these existing antibiotics are emerging. One solution could be to create new antibiotics with improved properties that can evade pathogen resistance mechanisms. However, non- and ribosomal peptide antibiotics are very complex structures that are difficult and expensive to produce by ordinary chemical methods. To address this, the Manchester team is using gene editing to engineer NRPS enzymes, swapping domains that recognize different amino acid building blocks, resulting in new assembly lines that can introduce new peptide products.
Michaelfield added: “We are now able to use gene editing to introduce targeted changes to complex NRPS enzymes, enabling the incorporation of alternative amino acid precursors into peptide structures. We are optimistic that our new approach could lead to new ways to improve Antibiotics much needed to combat emerging drug-resistant pathogens.”
The research paper has been published in Nature Communications “Gene editing enables rapid engineering of complex antibiotic assembly lines.”
Wei Li Thong et al, gene editing enables rapid engineering of complex antibiotic assembly lines, Nature Communications (2021). DOI: 10.1038 / s41467-021-27139-1
the quote: Scientists Produce New Antibiotics by Gene Editing (2021, November 25) Retrieved November 25, 2021 from https://phys.org/news/2021-11-scientists-antibiotics-gene.html
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