Partner 2

CoEBIO3 -Manchester logos

 CoEBio3 – University of Manchester

University of Manchester - Centre of Excellence for Biocatalysis, Biotransformations and Biocatalytic Manufacture (CoEBio3) http://coebio3-wp.eps.manchester.ac.uk is the UK's organization designed to provide a world-class scientific environment in which the necessary training, research and development can be carried out to create new biocatalyst-based processes to meet the changing needs of industry in the next 10-20 years. CoEBio3 will train graduate and postdoctoral scientists such that they possess the necessary combination of skills in chemistry, biology and engineering needed to support these changes.

CoEBio3 has particular strength in organic synthesis and brings the specialist expertise in developing new HTS methods suitable for identifying reactions suitable for identifying synthetically useful reactions.

The overall focus of the biocatalysis work is the discovery of efficient routes for the selective synthesis of chiral intermediates for pharmaceuticals or agrochemicals. In CoEBio3 research activities have also employed directed evolution together with high-throughput screening strategies to identify amine oxidases with improved catalytic activity and enantioselectivity towards target substrates of interest. Further work is currently underway applying directed evolution to other enzymes including P450 monooxygenases, alcohol oxidases and amino acid oxidases.

The Turner & Flitsch groups in CoEBio3 are located in the Manchester Interdisciplinary Biocentre (MIB; http://www.mib.ac.uk), which has its main facility at Manchester with an applied "genes to kilos" philosophy. The involvement of Industrial Affiliates results in very close relationships with the relevant industrial sector.

CoEBIO3 Manchester

P4FIFTY project in CoEBio3

In the search for new enzymes and biocatalysts, high-throughput screening methods for catalysis have a key role and they are necessary for screening libraries generated either from sampling the biosphere or from diverse generation methods. The technique suitable for HTS must be rapid and cost effective and reflecting the desired functions. The MIB team has successfully developed new fluorescence based HTS methods for several biocatalytic reactions. This HTS method will be used to screen bacterial, plant, fungal (and their mutants) P450 libraries for hydroxylation activity against a set of standard compounds which have to give specific reaction with human P450s. Another aspect of MIB efforts will be to develop P450s active in both conventional organic solvents and also alternative ones (such as fluorinated solvents) providing engineering solutions for large scale application to be investigated. The adaptation of existing HTS methods is associated with synthesis and testing new potential substrates.

 Prof Nick Turner PI

Nick obtained his DPhil in 1985 with Professor Sir Jack Baldwin and from 1985-1987 was a Royal Society Junior Research Fellow, spending time at Harvard University with Professor George Whitesides. He was appointed lecturer in 1987 at Exeter University and moved to Edinburgh in 1995. In October 2004 he joined Manchester University as Professor of Chemical Biology in the Manchester Interdisciplinary Biocentre. He is a Director of CoEBio3 and also a co-founder of Ingenza. He is a member of the Editorial Board of Chemical Communications. His research interests are in the area of biocatalysis with particular emphasis on the discovery and development of novel enzyme catalysed reactions for applications in organic synthesis, often employing directed evolution.

Project Title: Development of a broad substrate panel for screening against a wide range of novel P450s.

Research Objectives: To assemble structurally diverse panel of substrates and apply to the screening of P450s generated by other partners in order to characterise P450s with respect to substrate specificity. To collect this information and organise within the context of an easily searchable data-base.

Slavomíra Husárová after finishing her studies on Faculty of Pharmacy at Comenius University (Slovakia), in 2007 she begun a PhD funded by French Government scholarship under supervision of Dr. Mária Matulová (Slovak Academy of Sciences, Bratislava, Slovakia) and Dr. Anne-Marie Delort (Université Blaise Pascal, Clermont-Ferrand, France). Her PhD involved study of metabolism of bacteria isolated from cloud water, especially NMR structure elucidation of exopolysaccharides produced by bacterium under specific conditions, which could have great impact to the atmospheric processes. She currently works as a postdoctoral researcher for Prof. Nicholas Turner at the University of Manchester where her research focuses on the high-throughput screening methods development for study of cytochrome P450s biocatalysts for applications in industry as an Experienced Researcher in P4FIFTY.

Prof Sabine Flitsch PI

Sabine obtained her DPhil in 1985 with Professor Sir Jack Baldwin and from 1985-1989 was a DFG (Deutsche Forschungsgemeinschaft) Research Fellow, spending time at Massachusetts Institute of Technology with Professor H. Gobind Khorana. She was appointed University Lecturer and Fellow at St Hilda's College in 1989 at Oxford University and moved to Edinburgh in 1995. In October 2004 she joined Manchester University as Professor of Chemical Biology in the Manchester Interdisciplinary Biocentre. Her research interests are in the area of biocatalysis with particular emphasis on the discovery, development of novel enzyme catalysed reactions for applications in organic synthesis. The focus in the group is on P450-catalysed oxidations and modifications of carbohydrates and peptides.

Project Title: Development of high-throughput screening methods for assaying novel wildtype and engineered P450 monooxygenases

Research Objectives: To develop fluorescent panels of substrates and establish they can be used to interrogate libraries of P450 monooxygenases in order to be able to characterise their substrate specificity and selectivity.

Early Stage Researcher to start 1 October 2012: Anja Eichler, currently finishing her Diploma in Chemistry at University Freiburg, Germany