David Leak

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