The naturally produced Escherichia coli bacteria are difficult to work with as they grow in dense clumps that are incompatible with the automated robotic systems used for modern biotechnology research. By transferring the production machinery from the soil bacteria into E. coli, the Manchester team is now making this class of antibiotics accessible for much more rapid exploration.
This breakthrough could be vital for the ongoing combat against antimicrobial resistance, as recently developed automated robotics systems can now be used to create new antibiotics in a fast and efficient way.
In this work, published in the journal PLOS Biology, the group led by Professor Takano at The University of Manchester show the potential of this approach. By combining the bacterial production machinery with enzymes from plants and fungi, it was possible to produce new chemical compounds not previously seen in nature. Using this plug-and-play platform, it will now be possible to explore and engineer polyketides using robotic systems to develop new and diversified polyketides in an automated, rapid and versatile fashion.
Eriko Takano, Professor of Synthetic Biology said: “Nature is a huge treasure trove for powerful chemical compounds to treat a wide range of diseases. However, the most interesting chemicals often come from organisms that are difficult to work with in the laboratory.
“This has been a major bottleneck for our work on type II polyketides, a group of important chemicals, which are mostly produced by soil bacteria and other microorganisms that are challenging to grow. By successfully moving the production machinery for these compounds into the “laboratory workhorse” bacterium E. coli, we can finally produce and engineer type II polyketides in our rapid robotic systems.
“This not only allows us to trial new polyketides in an automated manner, but we will also be able to quickly rewrite the DNA sequences of the antibiotic biosynthesis pathways and combine them with new components from other organisms, such as medicinal plants and fungi, to produce variations on the antibiotic theme – including compounds that are not produced by the natural pathways, but may have enhanced or novel activities in the treatment of important diseases.”
It could take a person a whole year to make and test ten new potential antibiotics, but this automated robotic system can make thousands in that time. This would hugely decrease the time it takes for new antibiotics to reach patients, and provide the necessary agility to react to new pathogen strains and outbreaks.
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The University of Manchester Intellectual Property Limited (UMIP) assists in the commercialisation of any innovative technologies and processes that may be derived from collaborative research. UMIP has over a 20 year history of Intellectual Property (IP) commercialisation and works closely with MIB to ensure that any IP is fully developed to maximise technology transfer.
Spin out companies
Reacta Biotech Limited
Integrating food science with medicine
Reacta Biotech Limited was incorporated in June 2013 by its three founders: Professor Clare Mills (Professor of Molecular Allergology, based in the Manchester Institute of Biotechnology at the University of Manchester), Professor Ashley Woodcock (Professor of Respiratory Medicine at the University of Manchester and Clinical Director for the Directorate of Respiratory Medicine and Allergy at the University Hospital of South Manchester) and Peter McPartland (ex- SV Life Sciences). The Company’s seed capital round completed in April 2014, and second round funding completed in June 2015, have been supported by a small group of private investors.
Food allergy has become a major global health problem, affecting 17 million people in Europe alone, and around 220-250 million people worldwide. The Company’s first product will be an oral food challenge kit for the confirmation (diagnosis) of peanut allergy in allergic individuals. The current form of the oral food challenge test has been adapted from that used in the EU funded EuroPrevall project by Professor Clare Mills’ team. Through a multi-faceted agreement with the University, the Company has gained exclusive access to this early development work and the substantial body of knowhow that has been established around it.
Reacta Biotech’s proprietary technology consists of a stable food matrix, which will be prepared in a standardised process to the highest food and pharmaceutical manufacturing control standards. The products will have documented quantified levels of food allergen and will be manufactured under strictly controlled conditions, ensuring they meet the regulatory standard required for a clinical diagnostic. The food challenges will be formulated to blind allergen across a range of doses, with the effectiveness of blinding confirmed by sensory analysis. The matrix is reconstituted immediately prior to use to provide a mousse-style chocolate dessert. This represents a step-change in blinding peanut, delivering a palatable and pleasant oral food challenge material with a homogeneous and consistent allergen dose. The portfolio will be expanded to provide a range of challenge materials for patients with food allergy.
Website at: www.reactabiotech.co.uk
Spectromics was formed as a spin-out in April 2014 by the University’s technology transfer company UMIP within weeks of filing the key patent application relating to this rapid, phenotypic diagnostic. The company is developing the technology into a point-of-prescription test that fits within a typical 10 minute doctor – patient appointment. It will consist of a low cost, simple to use instrument used together with test specific disposable cartridges. Each cartridge will test the sample for infection susceptibility against a panel of candidate antibiotics routinely used for that particular infection. The founding scientists: Professor Roy Goodacre, of Manchester Institute of Biotechnology and Dr Mat Upton, of the School of Biomedical and Healthcare Sciences, Plymouth University, have worked on this technology for a number of years prior to company formation, they are now both Directors of the company.
Conformetrix Ltd was formed in 2007 by Dr Andrew Almond and Dr Charles Blundell and is focused on the optimisation of drug discovery and design using NMR-based technology to accurately solve bioactive three-dimensional molecular structures. Conformetrix won the Bionow Biomedical start-up of the year award for 2008 and Andrew was runner up in the 2009 “BBSRC Innovator of the Year” competition.
Pharmakure is a new drug discovery company focused on Alzheimer’s disease through the discovery of new uses for old drugs, offering great promise for delivering new therapeutic options to patient care. The founders of the company, Dr Farid Khan and Professor Andrew Doig have a successful track record and significant expertise in drug discovery and development in industry. PharmaKure has patented its first drug, PK-048, for the treatment of Alzheimer’s disease. PK-048 was first discovered in the 1980s, as a drug candidate for Parkinson’s disease, though it has never been previously tested for Alzheimer’s. The drug was tested in cell based assays and has demonstrated strong inhibition of β-amyloid cell toxicity. Importantly, previous data from animal trials have shown that the drug is orally active, non-toxic and crosses the blood-brain barrier in primate brains, a crucial requirement for an Alzheimer’s drug. In addition, PharmaKure’s approach of drug screening using cell-based models for AD has led to the identification of a number of promising hits and analogues which will further increase the company’s success & product portfolio. PharmaKure seeks further investment and pharma partnership to fund drug library screening; preclinical and early phase human trials.
In addition, MIB witnessed the formation of Discovery Biocatalysts in 2011.