Billions of years of evolution have resulted in a tremendous degree of diversity in nature. Species are out there that can produce unknown compounds that have enabled them to adapt and survive all sorts of aggressions in their environment. In the framework of the AGIR project carried out in collaboration with the Charles Viollette Institute (Lille, France) to implement an innovative strategy for the discovery of new antimicrobials, DEINOVE’s goal is to unearth the unexploited potential of rare microorganisms that might produce new antibiotic or antifungal compounds.
An integrated platform dedicated to discovering new antibiotics
A unique collection of rare bacterial strains
DEINOVE collects bacterial strains around the globe from hostile or challenging environments, such as caves or hot springs. These extreme conditions and/or competition between species selects robust organisms that produce original compounds still to be uncovered. To date, DEINOVE has isolated over 6’000 strains, and aims to expand its library with 10’000 additional bacterial strains within the next 5 years, by external collaborations or collection in specific environments conducive to antibiotic production.
Once collected from the environment, new bacterial strains need to be identified and grown in laboratory conditions for any downstream application. Earth samples first undergo a metagenomic analysis by high-throughput DNA sequencing, which identifies the species present, and guides the selection of specific strains. With a proven expertise in handling rare microorganisms, and in collaboration with specialist environmental microbiologists, the samples are cultivated under a variety of original growth conditions to expand and isolate the strains of interest.
Unlocking the potential of nature
Bacterial strains from DEINOVE’s collection undergo a thorough screening process to identify new antibiotic or antifungal activities. For each strain, several extracts are produced in parallel and under different extraction conditions to cover as much as possible the panel of compounds produced by the microorganism. A state-of-the-art robot enables the production of up to 150 samples a week to produce large-volume, completely standardized samples. Different dilutions of these high-content extracts are then used in highly sensitive in vitro screens for antimicrobial activity.
Once an activity has been detected, a combination of analytics and bioinformatics is used to identify the antibiotic structure responsible, as well as the genetic and metabolic pathways that are involved in its biosynthesis. To improve production of the compound, these pathways are optimised by genetically engineering the bacteria. Genetic engineering may also be used to modify the structure of the molecule and obtain a molecule with optimal performances. This involves the use of a custom-made computer-aided design software, jointly developed by DEINOVE and CAD4Bio, that performs in silico genetic engineering design and operates a robot to direct large-scale DNA cloning and strain construction. Subsequent screening then identifies the bacteria with the optimal genetic constructs for the production of the novel antimicrobial compound, a step that can be achieved up to a pre-industrial scale within the fermentation facilities of DEINOVE.
Together, the technology platforms at DEINOVE work towards the identification of new antimicrobial compounds, from the collection of rare microorganism to the development of new cultivating, screening and optimization methods.