The focus is on the efficient synthesis of chemicals and pharmaceuticals from renewable resources. This entails a multidisciplinary approach integrating biological and chemical catalysis with high throughput bioprocess design and scale-up.
The need to reduce our reliance on
petrochemical-derived materials and limit CO2 emissions is leading
us to explore the synthesis of chemicals and pharmaceuticals from renewable
feedstocks. Examples include sugar beet pulp, distillers’ grains, lignin and
algae-derived products made from light and CO2.
This multidisciplinary group focuses on the integration of biological and chemical catalysis for the synthesis of next generation chemicals and pharmaceuticals. In recent years the group has won major awards in the areas of Chemical Biology (Royal Society of Chemistry, 2010), Bioprocessing (Institution of Chemical Engineers, 2010) and for the translation of research into industrial practice (Evonik Science-to-Business award, 2008). Synthetic Biology underpins our research on the discovery and design of biological catalysts for industrial application. This includes aspects of metagenomics, enzyme, pathway and cellular engineering. A wide range of enzymes are under investigation including cytochrome P450s, norcoclaurine synthases, ketone reductases (KREDs), transketolases and transaminases. These are being expressed in a range of chasis organisms including Corynebacterium glutamicum, E. coli and Pichia pastoris.
In parallel we are interested in novel techniques for High Throughput Bioprocess Design, including microfluidic and automated microwell based systems, and novel engineering solutions to enhance reaction productivity e.g. chemo-enzymatic reaction cascades, multi-phase and photobioreactor design, continuous flow reactors and in-situ techniques for substrate supply/product removal. Mathematical modelling approaches aid in efficient experimental design (statistical Design of Experiments, DoE), biocatalyst design and evaluation (metabolic pathway and systems modelling), bioreactor design and scale-up (Computational Fluid Dynamics, CFD) and environmental impact analysis (Life Cycle Analysis, LCA).
Figure: Agricultural crops and their by-products represent sustainable feedstocks for chemical and pharmaceutical manufacture.
- Biocatalysis and
- Cell and enzyme engineering
- High throughput bioprocess design
- Bioreactor design and scale-up
Rios-Solis L, Morris P, Grant C, Odeleye AOO, Hailes HC, Ward JM, Dalby PA, Baganz F, Lye GJ. (2015) Modelling and optimisation of the one-pot multi-enzymatic synthesis of chiral alcohols based on microscale kinetic parameter determination. Chem. Engng. Sci., 122: 360-372. doi:10.1016/j.ces.2014.09.046
Du CJ, Rios-Solis L, Ward JM, Dalby PA, Lye GJ. (2014) Evaluation of Chromobacterium violaceum 2025 ω-transaminase for the bioconversion of lignin breakdown products into value-added chemicals: Synthesis of vanillylamine from vanillin. Biocat. Biotrans., 32: 302-313. doi:10.3109/10242422.2014.976632
Grant C, Deszc D, Wei, YC, Martinez-Torres, RJ, Phattaporn M, Foillard T, Sreenivasan R, Ward J, Dalby P, Woodley JM, Baganz F. (2014) Identification and use of an alkane transporter plug-in for applications in biocatalysis and whole-cell biosensing of alkanes. Sci. Rep., 4:5844. doi:10.1038/srep05844
Ojo EO, Auta H, Baganz F, Lye GJ. (2014) Engineering characterisation of a shaken, single-use photobioreactor for early stage microalgae cultivation of Chlorella sorokiniana. Bioresource Technol., 173: 367-375. doi:10.1016/j.biortech.2014.09.060
Sayer C, Martinez-Torres RJ, Richter N, Isupov MN, Hailes HC, Littlechild JA, Ward JM. (2014) The substrate specificity, enantioselectivity and structure of the (R)-selective amine: pyruvate transaminase from Nectria haematococca. FEBS Journal, 281, 2240-53. doi:10.1111/febs.12778
Abdul Halim A, Szita N, Baganz F. (2013) Characterization and multi-step transketolase-ω-transaminase bioconversions in an immobilized enzyme microreactor (IEMR) with packed tube. J Biotechnol. 168: 567-575. doi:10.1016/j.jbiotec.2013.09.001
Lawrence J, O’Sullivan B, Lye GJ, Wohlgemuth R, Szita N. (2013) Microfluidic multi-input reactor for biocatalytic synthesis using transketolase. J. Molecular Catalysis B: Enzymatic, 95: 111-117. doi:10.1016/j.molcatb.2013.05.016
Xu Y, Purton S, Baganz F. (2013) Chitosan flocculation to aid the harvesting of the microalga Chlorella sorokiniana Bioresource Technol 129: 296-301. doi:10.1016/j.biortech.2012.11.068
Baboo ZJ, Galman JL, Lye GJ, Ward JM, Hailes HC, Micheletti M. (2012) An Automated Microscale Platform for Evaluation and Optimisation of Oxidative Bioconversion Processes. Biotechnology Progress 28 (2), 392-405. doi:10.1002/btpr.1500
Grant C, Pinto AC, Lui HP, Woodley JM, Baganz F. (2012) Tools for characterising the whole-cell bio-oxidation of alkanes at microscale Biotech Bioeng 109: 2179–2189. doi:10.1002/bit.24512
Smith M, Chen B, Hibbert E, Kaulmann, U, Smithies K, Galman J, Baganz F, Dalby P, Hailes H, Lye G, Ward J, Woodley, J and Micheletti M. (2010) A multi-disciplinary approach toward the rapid and preparative scale biocatalytic synthesis of chiral amino alcohols: a concise transketolase/ω-transaminase-mediated synthesis of (2S,3S)-2-aminopentane-1,3-diol. Organic Process Research and Development, 14, 99-107. doi:10.1021/op900190y
Departmental staff involved include Dr Frank Baganz, Prof Paul Dalby, Dr Alex Kiparssides, Prof Gary Lye, Dr Martina Micheletti, Dr Darren Nesbeth, Dr Brenda Parker, Prof Nicolas Szita and Prof John Ward.
The multidisciplinary nature of this work entails partnerships with a wide range of academic collaborators across the UK and internationally. The group is also involved in leading the Biotransformation theme as part of the UK Catalysis Hub at the Harwell Research Complex. Key UK collaborators include Prof Helen Hailes and Dr Tom Sheppard (UCL, Chemistry), Prof David Leak (University of Bath), Prof Nilay Shah and Dr Kleo Kontoravdi (Centre for Process Systems Engineering, Imperial College), Prof Nicholas Turner (CoEBio3, University of Manchester)
International collaborators include Dr Martin Rebos (Slovak University of Technology), Prof John Woodley (Technical University of Denmark), Prof. Sergio Heurto-Ochoa (UAMI, Mexico), Prof Vlada Urlacher (University of Düsseldorf), Dr Dominik Gront (University of Warsaw), Dr Kai Sohn (Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB)