New mass-spectrometry technique boosts enzyme screening speed by up to 1000 times

New mass-spectrometry technique boosts enzyme screening speed by up to 1000 times

Scientists have developed  a new technique to screen engineered enzyme reactions, which could lead to faster and more efficient creation of medicines and sustainable chemicals.

Enzymes are proteins that catalyse chemical reactions, turning one substance into another. In labs, scientists engineer these enzymes to perform specific tasks like the sustainable creation of medicines, and materials. These biocatalysts have many environmental benefits as they often produce higher product quality, lower manufacturing cost, and less waste and reduced energy consumption. But to find ‘the one’, scientists must test hundreds of variants for their effectiveness, which is a slow, expensive, and resource-intensive process.

Research conducted by The University of Manchester in collaboration with AstraZeneca is changing this. The team developed a method for a technique that can test enzyme activity up to 1,000 times faster than traditional methods. The new method, developed over the last eight years and detailed in the journal Nature Protocols  is called DiBT-MS (Direct Analysis of Biotransformations with Mass Spectrometry).

Sabine Flitsch, Chair in Chemical Biology at The University of Manchester, said: “Current screening methods can really slow things down when we’re trying to find efficient biocatalysts because there are so many possible variations to test in an enzyme library. Some faster methods, like fluorescent microwell plates, do exist, but even then, you can hit a wall if your product doesn’t naturally fluoresce. That’s why there’s a real need for a quicker, simpler way to screen reactions. Our research shows how DiBT-MS can dramatically speed up the process, skipping the need for complicated sample preparation and using significantly less solvent and sample material, ultimately lessening our impact on the environment.”

It builds on an existing technology called DESI-MS (Desorption Electrospray Ionization Mass Spectrometry), a powerful tool that allows scientists to analyse complex biological samples without the need for extensive sample preparation. 

By making small adaptations to the technology, the scientists designed a protocol to directly analyse enzyme-triggered chemical reactions, known as biotransformations, in just minutes. The new method can process 96 samples in just two hours—tasks that would previously take days using older techniques.

It has also been optimised to allow the researchers to reuse sample slides multiple times improving testing efficiency and decreasing the use of solvents and plasticware.

The team has already successfully applied this technique to a range of enzyme-driven reactions, including those enzymes particularly valuable in the development of therapeutics.

Perdita Barran, Chair of Mass Spectrometry at The University of Manchester’s Institute of Biotechnology, said: “This approach opens up enzyme research to a much wider range of laboratories. And as the demand for sustainable and cost-effective chemical production and higher throughput assay screening grows, DiBT-MS will be an essential tool. Its simplicity, high throughput, and minimal sample preparation makes it an ideal choice for biochemists and chemical biologists who need a reliable, efficient way to conduct rapid and comprehensive enzyme screening.”

Looking ahead, The University of Manchester will continue to explore ways to boost partnerships between laboratories and tackle other challenges that often hinder collaboration, such as geographical barriers and limited funding.

This research was partly funded by a UKRI Prosperity Partnership grant in collaboration with AstraZeneca.

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About The University of Manchester 

The University of Manchester is recognised globally for its pioneering research, outstanding teaching and learning, and commitment to social responsibility. The Russell Group institution is ranked the 6^th best university in the UK and 52^nd in the world (Academic Ranking of World Universities). A truly international university, its community includes more than 44,000 students, 12,000 staff, and 550,000 alumni from 190 countries. Together, they are tackling the world’s biggest challenges – the University’s social and environmental impact is ranked in the top ten globally (Times Higher Education Impact Rankings). The University is a powerhouse of research and discovery; 26 Nobel laureates are among its former staff and students; and it was ranked fifth for research power – the quality and scale of research and impact – in the UK government’s Research Excellence Framework (REF) 2021. The institution is the most popular in the UK for undergraduate applications (UCAS 2023 cycle), and it is the most targeted university by the UK’s leading employers (The Graduate Market, 2024).  Learn more at www.manchester.ac.uk 

Mass spectrometry research in The University of Manchester is a fundamental and indispensable tool for researchers in the Life, Medical, Chemical, and Material sciences. Over the past 10 years we have received funding from UKRI for research in or dependent of mass spectrometry totalling £47M. This is the largest share of any UK HEI. At the University of Manchester, and at Manchester Foundation Trust, Mass Spectrometry plays a critical role in drug discovery, biomarker discovery, engineering biology, clinical diagnostics, as well as molecular, cellular, and structural biology research programs, and is a crucial technology for various 'omics' methods. The University of Manchester is home to numerous research laboratories actively engaged in mass spectrometry research, where novel methods in structural, omics, and clinical areas are continuously being developed. In the Faculty of Science and Engineering we have three full professors of Mass Spectrometry and many others for whom mass spectrometry is a cornerstone of their research.