Projects per year
Personal profile
Research interests
Current Research
We currently work on two themes: microbial metabolic engineering for production of chemicals from renewables, and bioprocessing for biopharmaceutical production. We also have long standing interests in applied biocatalysis. Much of our work is at the biology –chemistry/chemical engineering interface and has a strong focus in industrial biotechnology. We work closely with companies such as TMO Renewables and Fujifilm Diosynth and have links with a much wider network of industrial partners.
Metabolic engineering
Crop/waste lignocellulose conversion to fuels/chemicals involves inter-dependent steps: physical pretreatment; enzyme hydrolysis; fermentation and product recovery. Our work focuses on Geobacillus spp, bacteria which grow rapidly at 60-70oC on lignocellulose-derived oligomeric and monomeric carbohydrates. We worked with TMO Renewables in developing their “cellulosic” ethanol process using G. thermoglucosidasius (Cripps et al 2009). We are now creating a series of metabolic flux models, incorporating transcriptomic and 13C metabolic flux data to define strategies for making various chemicals from renewable feedstocks. We are also extending the catabolic versatility of this host to use complex carbohydrates in order to minimise the enzyme required for substrate pre-treatment, fundamental work which is being integrated with the use of real feedstocks (eg distillers dried grains, sugar beet pulp). This involves creation of new genetic tools employing a synthetic biology approach allowing the simple interchange of parts (Bartosiak-Jentys et al 2013). It also involves integrating substrate pre-treatment with the subsequent fermentation.
Bioprocessing
Pichia pastoris is a methylotrophic yeast commonly used for production of heterologous proteins including biopharmaceuticals. High heterologous protein titres can be obtained when cells are grown to very high cell density. However, the specific productivity is actually quite low and production is highly protein dependent. We are trying to unravel the rules which determine heterologous protein productivity in this host. This appears to be a combination of protein and host based factors
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Network
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Projects
Recovering value from contaminated plastic wastes
1/09/19 → 28/02/21
Project: Central government, health and local authorities
An Integrated Approach to Explore a Novel Paradigm for Biofuel Production from Lignocellulosic Feedstocks
Leak, D., Crennell, S. & Henk, D.
Biotechnology and Biological Sciences Research Council
1/03/17 → 31/03/21
Project: Research council
Integrated Energy Efficient Microwave and Unique Fermentation Processes for Pilot Scale Production of High Value Chemical from Lignocellulosic Waste
Henk, D., Leak, D. & Scott, R.
Engineering and Physical Sciences Research Council
1/03/16 → 30/10/20
Project: Research council
Decoding the carbon metabolic networks of Geobacillus thermoglucosidasius for industrial application
Leak, D., Shree, M. & Masakapalli, S.
1/10/18 → 1/02/19
Project: Research-related funding
Research Output
Pilot-scale production of xylo-oligosaccharides and fermentable sugars from Miscanthus using steam explosion pretreatment
Bhatia, R., Winters, A., Bryant, D. N., Bosch, M., Clifton-Brown, J., Leak, D. & Gallagher, J., 1 Jan 2020, In : Bioresource Technology. 296, 122285.Research output: Contribution to journal › Article
Open Access
1
Citation
(Scopus)
Polymers from sugars and unsaturated fatty acids: ADMET polymerisation of monomers derived from D-xylose, D-mannose and castor oil
Piccini, M., Leak, D. J., Chuck, C. J. & Buchard, A., 21 Apr 2020, In : Polymer Chemistry. 11, 15, p. 2681-2691 11 p.Research output: Contribution to journal › Article
Open Access
Bio-waste to resource: a review on mixed culture fermentation for medium chain carboxylic acids
De Groof, V., Lanham, A., Leak, D., Arnot, T. & Coma, M., 9 May 2019.Research output: Contribution to conference › Poster
Comparison of Nile red and cell size analysis for high throughput lipid estimation within oleaginous yeast.
Hicks, R., Chuck, C., Scott, R. J., Leak, D. & Henk, D., 1 Nov 2019, In : European Journal of Lipid Science and Technology. 121, 11, p. 1-8 8 p., 1800355.Research output: Contribution to journal › Article
Open Access
Engineering Escherichia coli for the production of butyl octanoate from endogenous octanoyl-CoA
Chacón, M. G., Kendrick, E. G. & Leak, D. J., 1 Jul 2019, In : PeerJ. 2019, 7, e6971.Research output: Contribution to journal › Article
Open Access
1
Citation
(Scopus)
Datasets
Nanofiltration and reverse osmosis membranes for purification and concentration of a 2,3-butanediol producing gas fermentation broth
Davey, C. (Creator), Patterson, D. (Supervisor) & Leak, D. (Supervisor), University of Bath, 14 Jul 2016
DOI: 10.15125/BATH-00212
Dataset
Dataset on experimental data available in the literature on "Medium chain carboxylic acids from complex organic feedstock by mixed culture fermentation"
De Groof, V. (Creator), Coma Bech, M. (Creator), Arnot, T. (Creator), Leak, D. (Creator) & Lanham, A. (Creator), University of Bath, 22 Jan 2019
DOI: 10.15125/BATH-00584
Dataset
Thesis
A Biophysical Approach to Understanding the Temperature-dependence of Enzyme Catalysis
Author: Jones, H., 2019Supervisor: Leak, D. (Supervisor) & Pudney, C. (Supervisor)
Student thesis: Doctoral Thesis › PhD
File
Addressing factors limiting the process efficiency of Pichia pastoris for the production of recombinant proteins
Author: Kendrick, E., 1 Sep 2016Supervisor: Leak, D. (Supervisor), Whitley, P. (Advisor) & Hodgson, I. (External person) (Supervisor)
Student thesis: Doctoral Thesis › PhD
File
Biophysical factors governing the structure, function, and dynamics of the NF-κB essential modulator protein (NEMO)
Author: Catici, A. M. D., 19 Jun 2019Supervisor: Leak, D. (Supervisor) & Pudney, C. (Supervisor)
Student thesis: Doctoral Thesis › PhD
File
Computational and experimental studies of mixing for industrial multiphase processes
Author: Maltby, R., 19 Feb 2020Supervisor: Chew, Y. (Supervisor) & Leak, D. (Supervisor)
Student thesis: Doctoral Thesis › PhD
File
Creation and evaluation of a pyruvate decarboxylase dependent ethanol fermentation pathway in Geobacillus thermoglucosidasius
Author: Buddrus, L., 1 Mar 2017Supervisor: Danson, M. (Supervisor) & Leak, D. (Supervisor)
Student thesis: Doctoral Thesis › PhD
File