Researchers are producing new antibiotics by gene editing


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Researchers have discovered a new way to produce complex antibiotics that utilize gene editing to reprogram pathways for future drugs that are urgently needed to combat antimicrobial resistance, treat neglected diseases, and tackle future pandemics.

Researchers from the University of Manchester have discovered a new way of manipulating important assembly-line enzymes in bacteria that could pave the way for a new generation of antibiotic treatments.

New research published today in Nature communication, describes how CRISPR-Cas9 gene editing can be used to create new non-ribosomal peptide synthetase (NRPS) enzymes that deliver clinically important antibiotics. NRPS enzymes are productive producers of natural antibiotics such as penicillin. Until now, however, manipulating these complex enzymes to produce new and more effective antibiotics has been a major challenge.

The UK government proposes that antimicrobial resistance (AMR) infections cause an estimated 700,000 deaths each year globally and is expected to rise to 10 million, costing the global economy $ 100 trillion, by 2050. AMR also threatens many of the UN’s goals for sustainable development (SDGs). ), with a further 28 million people who may be forced into extreme poverty by 2050 unless AMR is subdued.

The Manchester team says the gene editing process could be used to produce improved antibiotics and possibly lead to the development of new treatments that will help in the fight against drug-resistant pathogens and diseases in the future. Jason Micklefield, professor of chemical biology at the Manchester Institute of Biotechnology (MIB), UK, explains: “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 fast way to construct complex assembly line enzymes that can produce new antibiotic structures with potentially improved properties.”

Microorganisms in our environment, such as terrestrial bacteria, have developed non-ribosomal peptide synthetase enzymes (NRPS) that collect building blocks called amino acids for peptide products, which often have very potent antibiotic activity. Many of the most therapeutically important antibiotics used in the clinic today are derived from these NRPS enzymes (eg penicillin, vancomycin and daptomycin).

Unfortunately, deadly pathogens are emerging that are resistant to all of these existing antibiotics. One solution could be to create new antibiotics with improved properties that can evade the resistance mechanisms of the pathogens. However, the non-ribosomal peptide antibiotics are very complex structures which are difficult and expensive to manufacture by normal chemical methods. To address this, the Manchester team uses gene editing to construct NRPS enzymes, switching domains that recognize different amino acid building blocks, leading to new assembly lines that can deliver new peptide products.

Micklefield added: “We are now able to use gene editing to introduce targeted changes to complex NRPS enzymes, making it possible to incorporate alternative amino acid precursors into peptide structures. We are optimistic that our new approach may lead to new ways of produce improved antibiotics that are urgently needed to combat new drug-resistant pathogens. “

The research paper is published in Nature communication as “Gene editing enables rapid construction of complex antibiotic assembly lines.”

Researchers are discovering a new path to antibiotics through gene editing

More information:
Wei Li Thong et al., Gene editing enables rapid construction of complex antibiotic assembly lines, Nature communication (2021). DOI: 10.1038 / s41467-021-27139-1

Citation: Researchers produce new antibiotics by gene editing (2021, 25 November) retrieved 25 November 2021 from

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