Synthetic biology is the engineering of biology. We aim to create complex, biologically based and biologically inspired systems which display functions that assist and enhance bioprocessing; and to create new pathways, molecules and genetic networks.
The building of new biological entities such as metabolic pathways, modified cells that enhance bioprocessing and self assembling phage derivatives that can be used as templates for building in bio-inspired nanobiotechnology are some of the examples we are researching in our synthetic biology research programmes.
Building a novel biosynthetic pathway for bioactive compounds
We have engineered the standard E. coli chassis to degrade its own RNA at lysis and this removes the need for adding exogenous RNAse in subsequent downstream processing during plasmid DNA production. A further modification where we expressed a nuclease that destroyed both RNA and DNA has created a chassis that has enhanced processing characteristics for protein manufacture. We are currently extending this concept of cell engineering for process enhancement to enhance secreted protein production, engineer other chassis organisms such as Pseudomonas putida and CHO cells and to remove other contaminants from process streams.
Synthetic Biology is the basis for our work on the discovery and design of biological catalysts for industrial application. We use genome mining, metagenomics and synthetic gene design to create the biocatalysts. We build these into de novo designed novel pathways for the production of chiral compounds and high value fine chemicals. We are creating novel routes to alkaloids and have compounds that are active as antimicrobials. We use a range of chassis organisms including Corynebacterium glutamicum, E. coli, P. putida and Pichia pastoris.
- Chassis (host cell) engineering and development
- De novo pathway design and construction
- Biomass to fine chemicals
- Synthetic genetic networks
- Phage nano-biotechnology
- Genome ablation
- Synthetic biology to enhance and redefine bioprocessing
Lichman BR, Gershater MC, Lamming ED, Pesnot T, Sula A, Keep NH, Hailes HC, Ward JM. (2015) ‘Dopamine-first’ Mechanism Enables Rational Engineering of Norcoclaurine Synthase (NCS) Aldehyde Activity Profile. FEBS Journal, 282, 1137-1151. doi:10.1111/febs.13208
Lichman BR, Lamming ED, Pesnot T, Smith JM, Hailes HC, Ward JM. (2015) One-pot triangular chemoenzymatic cascades for the synthesis of chiral alkaloids from dopamine. Green Chem., 17, 852-855. doi:10.1039/C4GC02325K
Borg YB, Ekkehard U, Afnan A, Alsaedi A, Nesbeth D, Zaikin A (2014) Complex and unexpected dynamics in simple genetic regulatory networks. International Journal of Modern Physics B, 28 (14), doi:10.1142/S0217979214300060
Grant C, Dawid Deszcz D, Wei YC, Martinez-Torres RJ, Morris P, Folliard T, Rakesh Sreenivasan R, Ward JM, Dalby P, Woodley JM and Baganz F. (2014) Identification and use of an alkane transporter plug-in for applications in biocatalysis and whole-cell biosensing of alkanes. Nature Sci Rep., 4, 5844. doi:10.1038/srep05844
Herschy B, Whicher A, Camprubi E, Watson C, Dartnell L, Ward J, Evans JR, Lane N. (2014) An origin-of-life reactor to simulate alkaline hydrothermal vents. J Mol Evol., 79, 213-27. doi:10.1007/s00239-014-9658-4
Richter N, Simon RC, Kroutil W, Ward JM, Hailes HC. (2014) Synthesis of pharmaceutically relevant 17-a-amino steroids using an w-transaminase. Chem. Commun., 50, 6098-6100. doi: 10.1039/C3CC49080G
Sehl T, Hailes HC, Ward JM, Menyes U, Pohl M and Rother D. (2014) Efficient 2-step biocatalytic strategies for the synthesis of all nor(pseudo)ephedrine isomers. Green Chem., 16, 3341-3348. doi:10.1039/c4gc00100a
Branston SD, Stanley EC, Ward JM and Keshavarz-Moore E. (2013) Determination of the survival of bacteriophage M13 from chemical and physical challenges to assist in its sustainable bioprocessing. Biotech. Bioproc. Eng., 18, 560-566. doi:10.1007/s12257-012-0776-9
Halim AA1, 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, 567-75. doi:10.1016/j.jbiotec.2013.09.001
Horst I, Parker BM, Dennis JS, Howe CJ, Scott SA, Smith AG. (2012) Treatment of Phaeodactylum tricornutum cells with papain facilitates lipid extraction. J Biotechnol., 162, 40-49. doi:10.1016/j.jbiotec.2012.06.033
Nesbeth DN, Perez-Pardo MA, Ali S, Ward, JM, Keshavarz-Moore E. (2012) Growth and productivity impacts of periplasmic nuclease expression in an Escherichia coli Fab' fragment production strain. Biotechnol Bioeng, 109 (2) 517-527. doi:10.1002/bit.23316
Departmental staff involved in the Synthetic Biology research programmes are: Dr Darren Nesbeth, Dr Frank Baganz, Prof Paul Dalby, Prof Gary Lye, Prof Eli Keshavarz-Moore, Dr Brenda Parker, Dr Alex Kiparssides, Dr Tarit Mukhopadhyay and Prof John Ward.
There is a synthetic biology network across UCL, Synbion, and we collaborate with Prof Helen Hailes (UCL, Chemistry), Prof Stefan Howorka (UCL, Chemistry), Dr Vitor Pinheiro (UCL, SMB), Dr Renos Savva (Birkbeck), Dr Geraint Thomas (UCL, CDB), Dr Chris Barnes (UCL,CDB), Prof Alexey Zaikin (UCL, Maths), Prof David Leak (University of Bath), Prof Nicholas Turner (CoEBio3, University of Manchester), Prof Tim Dafforn (University of Birmingham) and others.