The Bioconversion - Chemistry - Engineering Interface Programme (BiCE)
The mutli-disciplinary Bioconversion-Chemistry-Engineering Interface (BiCE) programme brings together academics from three UCL faculties interested in the synthesis of the next generation of complex chiral pharmaceuticals. The BiCE programme has two strategic goals:
- The acceleration of biocatalytic process creation and optimisation
- The integration of biocatalysis within atom efficient multi-step chemical syntheses
Key research areas designed to meet these goals are listed below. Collaborative doctoral and post-doctoral projects are currently underway in each of these areas funded by a combination of BBSRC, EPSRC and Technology Strategy Board awards.
- Chemistry studies for the better integration of chemical and biocatalytic routes to single isomer chiral synthons
- Microbial libraries and sequence database mining for identification of novel enzyme activities
- Novel directed evolution approaches to yield step changes in enzyme stability, selectivity and activity enhancement
- Cell engineering for the creation of de novo metabolic pathways and more robust cellular biocatalysts
- Automated microscale processes for rapid process creation and optimisation
- New microfluidic and microwell technologies for evaluation of multistep chemoenzymatic process options
- Modelling tools to set biocatalyst engineering targets and to predict large scale process performance
BiCE programme focuses on the linkage of novel chemistries with
advanced bioconversions capable of stereoselective carbon-carbon bond
formation, amine group addition and selective hydroxylation and
A multi-disciplinary group of UCL academics with a long history of collaboration contribute to delivery of the BiCE goals. These include Prof. Gary Lye (process modelling and scale-up), Prof. John Ward (Department of Biochemistry and Molecular Biology; enzyme discovery and cell engineering), Dr Helen Hailes (Department of Chemistry; chemo-enzymatic synthesis and chiral analysis), Dr Frank Baganz (metabolic modelling and engineering), Professor Paul Dalby (enzyme engineering and evolution), Dr Martina Micheletti (microscale processing and automation) and Dr Nicolas Szita (microfabrication and microfluidic devices).
A consortium of 13 companies provides an industrial Steering Group to assist in the direction and management of the programme. Current steering group members include Almac (UK), Alphamerix (UK), Astra Zeneca (UK), Codexis (USA), DSM (NL), Evonik-Degussa (DE), HEL (UK), Lonza (CH), Merck & Co (USA), Novacta (UK), Sigma-Aldrich (CH), Sirus Analytical (UK) and Tecan (UK).
Selected BiCE Publications
The UCL team have a proven track record of multidisciplinary collaboration and co-publication. Listed below are selected recent publications that contribute to delivery of the BiCE goals. Authors indicated in bold represent members of the staff team.
(i) Chemo- enzymatic integration and high throughput analysis
Aucamp, J.P., Martinez-Torres, R.J., Hibbert, E.G. and Dalby, P.A. (2007). A microplate-based evaluation of complex denaturation pathways: Structural stability of E. coli transketolase. Biotech. Bioeng., In press.
Dalby, P.A. , Lye, G.J. and Woodley, J.M. (2005) One-pot synthesis and the integration of chemical and biocatalytic conversions. In Handbook of Chiral Chemicals, 2nd ed., Ed. Ager, D.J., Pp 419-428, CRC Press, Boca Raton.
Hailes, H.C., Dalby, P.A. , Woodley, J. M. (2007) Integration of biocatalytic conversions into chemical syntheses. J. Chem. Tech. Biotech., 82: 1063-1066.
Miller, O.J., Hibbert, E.G., Ingram, C.U., Lye, G.J. and Dalby, P.A. (2007) Optimisation and evaluation of a generic microplate-based HPLC screen for transketolase activity. Biotech. Lett., 29: 1759-1770.
Smith, M.E.B., Kaulmann, U., Ward, J.M. and Hailes, H.C. (2006) A colorimetric assay for screening transketolase activity. Biorg. Med.Chem., 14: 7062-7065.
(ii) Enzyme recruitment, evolution and cell engineering
Hibbert, E.G., Baganz, F., Hailes, H.C., Ward, J.M., Lye, G.J., Woodley, J.M. and Dalby, P.A. (2005). Directed evolution of biocatalytic processes, Biomolec. Engng., 22: 11-19.
Hibbert, E.G., Senussi, T., Costelloe, S.J., Lei, W., Smith, M.E.B., Ward, J.M., Hailes, H.C., and Dalby, P.A. (2007) Directed evolution of transketolase activity on non-phosphorylated substrates. J. Biotechnology, 131: 425-432.
Kaulmann, U, Smithies, K., Smith, M.E.B., Hailes, H. C and Ward, J.M. (2007) Substrate spectrum of ω-transaminase from Chromobacterium violaceum DSM30191 and its potential for biocatalysis. Enz. Microb. Technol., 41, 628-637.
Ingram, C.U., Bommer, M., Smith, M.E.B., Dalby, P.A., Ward, J.M., Hailes, H., and Lye, G.J. (2007) One-pot synthesis of amino diols using a de-novo transketolase and ß-alanine:pyruvate transaminase pathway in Escherichia coli. Biotech. Bioeng., 96: 559-569.
(iii) Microscale tools for rapid process optimisation and design
Ferreira-Torres, C., Micheletti, M. and Lye, G.J. (2005) Microscale process evaluation of recombinant biocatalyst libraries: Application to Baeyer-Villiger monooxygenase catalysed lactone synthesis. Bioproc. Biosystems Eng. , 28: 83-93.
Gill, N.K., Appleton , M., Baganz, F. and Lye, G.J. (2007) Design and instrumentation of a novel miniature bioreactor system for high throughput fermentation optimisation. Biochem. Engng. J., in press.
Micheletti, M., Barrett, T., Doig , S.D. , Baganz, F., Levy, M.S., Woodley, J.M. and Lye, G.J. (2006) Fluid mixing in shaken bioreactors: Implications for scale-up predictions from microlitre scale microbial cultures. Chem. Eng. Sci ., 61: 2939-2949.
Micheletti, M. and Lye, G.J. (2006) Microscale bioprocess optimisation. Curr. Opin. Biotech., 17: 611-618.
Szita, N. , Boccazzi, P., Zhang, Z., Boyle, P., Sinsky, K.F., Jensen, K. (2005) Development of a multiplexed microbioreactor system for high throughput bioprocessing. Lab on a Chip, 5: 819-826.
(iv) Numerical and modelling tools for process evaluation
Chen, B.H., Baganz, F. and Woodley J.M. (2007) Modelling and optimisation of a transketolase mediated carbon-carbon bond formation reaction. Chem. Eng. Sci., 62: 3178-3184.
Chen, B.H., Sayar, A., Kaulmann, U., Dalby, P.A., Ward, J.M. and Woodley, J.M. (2006) Reaction modelling and simulation to assess the integrated use of transketolase and ω-transaminase for the synthesis of an aminotriol. Biocat. & Biotrans., 24: 449-457.
Islam, R.S., Tisi, D., Levy, M.S. and Lye, G.J. (2007) Framework for the rapid optimisation of soluble protein expression in Escherichia coli combining microscale experiments and statistical experimental design. Biotech. Progr., 23: 785-793.
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