The collaborative efforts of a team led by Professors Sang Yup Lee, Shi Chen, and Lianrong Wang have effectively devised a genome engineering-based systematic technique for creating phage resistant Escherichia coli strains.
This study by Xuan Zou and colleagues was released in Nature Communications in August 2022 and highlighted by the editors of Nature Communications.
The collaboration between the First Affiliated Hospital of Shenzhen University, the KAIST Department of Chemical and Biomolecular Engineering, and the School of Pharmaceutical Sciences at Wuhan University has made significant strides in the metabolic engineering and fermentation industries by addressing a significant issue of phage infection leading to fermentation failure.
The development of microbial cell factories to manufacture numerous bioproducts, including chemicals, fuels, and materials, has been made possible by the extremely interdisciplinary discipline of systems metabolic engineering.
This has helped to reduce the effects of global resource depletion and climate change. Given its numerous uses in the bio-based manufacturing of a variety of chemicals and materials, Escherichia coli is one of the most significant bacterial species.
A highly optimized and well-characterized cell factory will play a vital role in transforming inexpensive and easily accessible raw materials into products of significant economic and commercial value with the development of tools and techniques for systems metabolic engineering utilizing E. coli.
The persistent issue of phage infection in fermentation, however, has a catastrophic effect on host cells and jeopardizes the efficiency of bacterial bioprocesses in biotechnology facilities, which can result in widespread fermentation failure and incalculable economic loss.
To address bacteriophage contamination in industrial-scale fermentation, host-controlled defense systems can be turned into efficient genetic engineering solutions; nevertheless, most of the resistance mechanisms only narrowly restrict phages and their impact on phage contamination will be limited.
There have been efforts to create a variety of skills or defense mechanisms for antiviral defense or environmental adaption. The team’s collaborative efforts developed a new type II single-stranded DNA phosphorothioation (Ssp) defense system derived from E. coli 3234/A, which can be used in multiple industrial E. coli strains (e.g., E. coli K-12, B and W) to provide broad protection against various types of dsDNA coliphages.
Additionally, they created a methodical approach to genome engineering that involves the simultaneous genomic integration of the Ssp defense module and alterations in elements crucial to the phage life cycle.
By employing this technique, it is possible to turn strains of E. coli that are very vulnerable to phage attack into hosts with potent restriction effects on the studied bacteriophages. This gives hosts robust defenses against a variety of phage infections without interfering with bacterial development or regular bodily processes.
More crucially, even under extreme phage cocktail challenges, the resulting designed phage-resistant strains continued to be able to produce the necessary chemicals and recombinant proteins, offering vital defense against phage attacks.
This represents a significant advance since it offers a methodical approach to creating phage-resistant bacterial strains, particularly those used in industrial bioproduction, which can shield cells against a variety of bacteriophages.
Given that this engineering method works with a variety of E. coli strains, it can be broadly applied to other bacterial species and industrial applications. This will be of considerable interest to academic and industrial researchers alike.
