Antibiotics are one of the scientific innovations that changed the world back in the 20th century. However, the overuse and the misuse of antibiotics during the years have fed the emergence of multi-resistant bacteria. As a consequence, “superbug” infections are one of the most urgent threats that humankind has to fight. Since the discovery of penicillin in 1928, researchers have been immersed in the task of finding other antibiotics, and currently there are over 100 of them available in the market. Regretfully, as we explained in a previous post, the discovery of new antibiotics has decreased drastically: the last one, ceftazidime, was released to the market in 2015.
Very often, scientists turn their heads to nature to look for the solution for a challenge. In fact, 50% of all drugs are derived from or inspired by natural sources. Microbes have contributed with a great amount of antibiotics, as many of them naturally produce antimicrobial substances to inhibit or kill other microorganisms. Today, we bring you a fellow European project that aims to harness these skilled bacteria and turn them into microbial cell factories of high-value antibiotics: Thoroughly Optimised Production Chassis for Advanced Pharmaceutical Ingredients or TOPCAPI.
Among the millions of microorganisms on Earth, the project has focused on actinomycetes. And it isn’t an arbitrary choice: actinomycetes have produced over 80% of the natural products that have inspired commercially used antibiotics. These microbes are evolutionarily optimised to make compounds that can help in the battle against multi-resistant infections.
This four-year project aims to exploit the biosynthetic power of two actinomycetes: Streptomyces coelicolor and Streptomyces rimosus. The objective is to produce antimicrobial compounds at an industrial level. However, while these bacteria synthesise many antibiotics naturally, there is still no strain efficient enough to produce antibiotics commercially. TOPCAPI will leverage on synthetic biology tools to design metabolic pathways that produce effective antibiotics and optimise the expression of these pathways, to achieve viable production levels. Furthermore, the project aims to set a toolbox for the engineering of actinomycetes as general cell factories for other high added-value compounds.
The starting point of TOPCAPI is to gather an exhaustive data collection about the species of interest, using genome sequencing and omics techniques. Then, they will analyse and model the metabolic pathways that the microbes would use to produce the antibiotic compounds. This information will be applied to engineer the bacterial strains by using novel genome editing technologies such as CRISPR/Cas. This process will be repeated to optimise the soon-to-be microbial factories. Once the strains are correctly modified, the project will validate their production capacity of the interest compounds and exploit these microbial cell factories industrially.
To carry out such as multidisciplinary strategy, TOPCAPI brings together researchers from across Europe with different expertise areas of synthetic biology and biotechnology. The project also involves academic institutions and SMEs, to ensure there is a balance between scientific findings and industrial application.
The project started at the beginning of 2017, so we are already looking forward to seeing some of their results! Stay tuned to their Twitter for more information!