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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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Projects 2012 2021

Biofuels
Yeast
Fermentation
Feedstocks
Oligosaccharides

A Network of Integrated Technologies: Plants to Products

Leak, D.

10/03/149/03/19

Project: Research council

directory
economic growth
stakeholder
life cycle
student

Research Output 1999 2018

Continuous enzymatic hydrolysis of sugar beet pectin and L-arabinose recovery within an integrated biorefinery

Cárdenas-Fernández, M., Hamley-Bennett, C., Leak, D. J. & Lye, G. J., 1 Dec 2018, In : Bioresource Technology. 269, p. 195-202 8 p.

Research output: Contribution to journalArticle

Open Access
Sugar beets
Arabinose
Enzymatic hydrolysis
sugar beet
hydrolysis

Crystal structure of an inferred ancestral bacterial pyruvate decarboxylase

Buddrus, L., Andrews, E. S. V., Leak, D., Danson, M., Arcus, V. L. & Crennell, S., 1 Mar 2018, In : Acta Crystallographica Section F:Structural Biology Communications. 74, 3

Research output: Contribution to journalArticle

Open Access
Pyruvate Decarboxylase
pyruvates
enzymes
Crystal structure
Bins

Medium chain carboxylic acids from COD-rich food waste as sole substrate

De Groof, V., Arnot, T., Lanham, A., Coma, M. & Leak, D., 16 Jul 2018.

Research output: Contribution to conferenceAbstract

4 Citations

An integrated biorefinery concept for conversion of sugar beet pulp into value-added chemicals and pharmaceutical intermediates

Cárdenas-Fernández, M., Bawn, M., Hamley-Bennett, C., Bharat, P. K. V., Subrizi, F., Suhaili, N., Ward, D. P., Bourdin, S., Dalby, P. A., Hailes, H. C., Hewitson, P., Ignatova, S., Kontoravdi, C., Leak, D. J., Shah, N., Sheppard, T. D., Ward, J. M. & Lye, G. J., 1 Sep 2017, In : Faraday Discussions. 202, p. 415-431

Research output: Contribution to journalArticle

Open Access
sugar beets
Sugar beets
Pulp
Pharmaceutical Preparations
cellulose
6 Citations

Centrifugal partition chromatography in a biorefinery context: Optimisation and scale-up of monosaccharide fractionation from hydrolysed sugar beet pulp

Ward, D. P., Hewitson, P., Cárdenas-Fernández, M., Hamley-Bennett, C., Díaz-Rodríguez, A., Douillet, N., Adams, J. P., Leak, D. J., Ignatova, S. & Lye, G. J., 12 May 2017, In : Journal of Chromatography A. 1497, p. 56-63 8 p.

Research output: Contribution to journalArticle

Open Access
Sugar beets
Beta vulgaris
Monosaccharides
Fractionation
Chromatography

Thesis

Addressing factors limiting the process efficiency of Pichia pastoris for the production of recombinant proteins

Author: Kendrick, E., 1 Sep 2016

Supervisor: Leak, D. (Supervisor), Whitley, P. (Advisor) & Hodgson, I. (External person) (Supervisor)

Student thesis: Doctoral ThesisPhD

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Creation and evaluation of a pyruvate decarboxylase dependent ethanol fermentation pathway in Geobacillus thermoglucosidasius

Author: Buddrus, L., 1 Mar 2017

Supervisor: Danson, M. (Supervisor) & Leak, D. (Supervisor)

Student thesis: Doctoral ThesisPhD

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Esterification as a strategy for the detoxification of value compounds in Escherichia coli

Author: Chacon, M., 30 Sep 2017

Supervisor: Leak, D. (Supervisor) & Bolhuis, A. (Supervisor)

Student thesis: Doctoral ThesisPhD

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Genomic analysis and metabolic modelling of Geobacillus thermoglucosidasiusNCIMB 11955

Author: Lisowska, B., 29 Jun 2016

Supervisor: Leak, D. (Supervisor)

Student thesis: Doctoral ThesisPhD

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Lower Energy Recovery of Dilute Organics from Fermentation Broths

Author: Davey, C., 3 Mar 2017

Supervisor: Patterson, D. (Supervisor) & Leak, D. (Supervisor)

Student thesis: Doctoral ThesisPhD

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