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Nearly every challenge facing our world has already been solved by nature’s vast reservoir of microorganisms, or microbes, which perform all kinds of reactions that could prove useful to industry.
However, sifting through the collective genetic material from microbes to find and harvest the enzymes responsible for those reactions is an overwhelming task. Existing robotic-screening tools are relatively slow. They demand a lot of manpower and capital expenditure, which makes them extremely expensive and largely inaccessible to most researchers.
The EU-funded METAFLUIDICS project takes a new approach to investigating microbes found in the world’s most extreme environments, focussing on uncovering industrially relevant enzymes. Instead of culturing separate microbes gathered from an environmental sample, such as from the bottom of a lake, and studying them individually, the team is developing technology that can study their genetic material – their metagenome – all at once.
The methodology can analyse 100 million DNA fragments a day, automatically deciding if a sought-after enzyme is encoded in any one of the fragments. Their approach is 1 000 times faster and up to a million times cheaper than conventional analytical techniques. The effectiveness and versatility of the technology means that it has the power to discover hundreds of new enzymes in just one week.
The platform has already been used to identify useful enzymes from a variety of microorganisms. Examples include an enzyme from microbes found in garden soil that degrades plastic bottles, and enzymes from high-altitude-dwelling microbes that could be bred into plants to offer greater UV-resistance. This discovery could improve crop growth at higher altitudes and support long-term space missions.
‘Other partners have used the technology to better understand how microorganisms shape their environment and react to changing conditions, such as increasing temperatures and floods,’ says project coordinator Aurelio Hidalgo of the Universidad Autónoma de Madrid in Spain.
‘We can also use it to study intestinal bacteria and the nature of their relationships with each other and with their hosts, to understand more about the factors that favour a healthy gut.’
Screening for useful genes
The project’s key innovation is its microfluidic technology which separates single DNA fragments into microscopic droplets. Once isolated, these droplets are combined with reagents which drive these genes to produce their corresponding enzymes. Using a laser beam and fluorescent markers, METAFLUIDICS researchers are then able to detect and select droplets with positive reactions to a certain enzyme. The system screens up to 5 000 droplets per second.
The project has required the development of novel biological and bioinformatic technologies. Biological tools have been designed to decode DNA from a variety of extreme environments, regardless of whether samples come from a saltern with barely any available water, a steaming hot spring, or plants growing in Antarctica.
Bioinformatic tools developed during METAFLUIDICS are being used to build a catalogue of potentially useful microbial enzymes and to characterise the respective DNA sequences to shed light on their relationships, similarities and differences.
Rapid reaction
‘Our partners are commercialising microfluidic technology and services, and are considering licensing their discoveries to companies,’ says Hidalgo. ‘Other industrial partners have already put enzymes and software solutions developed during this project on the market. This is an unusually fast uptake for a biotechnology research project.’
For instance, INSAT has identified enzymes that break down and synthesise carbohydrates, which could be used to manufacture bioactive compounds that promote gut health and to develop texture modifiers for the food industry. Prozomix has increased their portfolio by more than 400 new enzymes for biocatalysis and industrial applications, and QIAGEN has commercialised a software tool called the CLC Genomics Workbench, which already has around 1 500 users.