To use novel Ultra Scale-Down methods to speed the creation and scale-up of processes for fermentation based industrial enzyme manufacture thereby increasing efficiency and productivity.

To use novel Ultra Scale-Down methods to speed the creation and scale-up of processes for fermentation based industrial enzyme manufacture, increasing efficiency and productivity.

"Biocatalysts Ltd are an SME located in Cardiff UK. Using microbial fermentation technology, we manufacture high-value enzymes that are sold into the following market applications: (i) used as processing aids in the manufacture of pharmaceutical intermediates (ii) used as processing aids in the manufacture of food ingredients (iii) used for DNA processing in Life Science applications. We have several microbial platforms that we use to manufacture recombinant enzymes incorporating both bacteria and yeasts. When we develop a strategic enzyme product for a new market or a novel enzyme product for a customer project we perform a diligent assessment of the enzyme with our Design for Manufacture process. This is aimed at maximising the probability that if we can make the enzyme at laboratory scale then we will be able to scale-up to large scale commercially viable fermentations and downstream processes to meet cost targets. Some enzymes are more suitable for expression in yeast than bacteria and our current default yeast manufacturing platform is in _Pichia pastoris_. The most widely used expression system in _Pichia_ at both the academic and commercial scale involves the use of Methanol as an inducer for the high-level expression of the enzyme (protein). Large-scale use of methanol in a manufacturing context is fraught with economic, health and safety and potential environmental constraints. Consequently Biocatalysts is currently limited to methanol-induced Pichia fermentations to a scale of 500 L. We are currently expanding our manufacturing capacity over a 2 year plan to 8,000 L. It is prohibitively expensive to equip such a facility with the capacity to work with methanol at this fermentation scale. Currently we have 3 enzyme products produced at large-scale in _Pichia_ with methanol induction, so consequently we are obliged to export this business to a partner company in Europe. Therefore, this project is aimed at developing a cost effective, high yielding methanol-free expression system for commercial manufacturing scale in the yeast _Pichia pastoris_ to allow our business to expand in this area in the UK."

Enzymes are biological molecules that facilitate chemical reactions in living cells. Many products in the fine chemical, food, flavour & fragrance, pharmaceutical and biotherapeutic industries use enzymes in their manufacturing processes. The majority (more than 75%) of enzymes currently used in industrial processes are hydrolytic in action. Among these, lipases and phospholipases are the enzymes that are used for lipid modifications. Phospholipases represent a versatile biocatalyst in various industrial applications. This project is aimed at producing phospholipases in simple microbial production hosts using recent technological advances in molecular biology in order to produce unique enzymes for the industrial biocatalysis market.

Only a tiny fraction (~1%) of all microorganisms can currently be grown in the laboratory and hence have their DNA sequenced. Thus, there is a huge wealth of genetic sequence data still to be discovered from environmental samples of the remaining 99% of uncultured microorganisms. The field of metagenomics directly samples microorganisms living in the environment, thereby avoiding the need for laboratory culturing before DNA sequencing. Metagenomics projects can yield very large amounts of DNA sequence data and the major bottleneck to exploiting this data for enzyme discovery is the actual data analysis. The objective of this project between Biocatalysts Ltd and EMBL-EBI is to develop a novel and unique data analysis software platform, MetXtra, for the rapid and efficient identification of completely novel enzymes for Industrial Biotechnology (IB) applications from large metagenomic DNA sequence libraries.

Enzymes are biological molecules that facilitate chemical reactions in living cells. Many products in the food, fine chemical, flavour & fragrance, pharmaceutical and biotherapeutic industries use enzymes in their manufacturing processes. Many enzymes on the market are isolated from their original wild-type organism, many more need to be produced in a different host organism that is more suitable for large-scale industrial production and is capable of providing commercially viable yields of the enzyme. To optimise the level of production of the enzyme is time consuming and costly and often results in failure to achieve commercial yield targets due to the inherent biology of the host and the enzyme. Therefore, this project will develop a broad-host range expression system for expressing any new enzyme in a selection of industrially compatible microorganisms and assessing enzyme production in these multiple hosts prior to selecting the one that provides the highest yields for that enzyme.

This project is designed to manufacture a useful class of organic chemicals, used in paint formulations, starting with a waste by-product from the chemical industry and transforming it to the desired material by use of biocatalysis. The current chemical route employs caustic soda and sulphuric acid, and as well as producing the desired product, also co-produces a large amount of waste. The biocatalytic route is very materials-efficient and also much more energy-efficient. The project brings together the University of Northumbria, an acknowledged centre of excellence in Biotransformations, Biocatalysts Ltd, a well-established manufacturer of biocatalysts for industrial use, CPI, a UK based technology innovation centre and part of the High Value Manufacturing Catapult providing open access facilities for the development and scale-up of biotechnology based processes, Beckers, a multinational Paint Manufacturer, who specialise in Coil Coatings and Chemoxy International Ltd, a medium sized UK chemical company who currently manufactures a range of eco-friendly solvents for use in surface coatings applications.

A consortium comprising of Aesica Pharmaceuticals, Biocatalysts Ltd, CatScI Ltd and Charnwood Technical Consulting has been established as part of the Sustainable High-Value Chemical Manufacture through Industrial Biotechnology (IB) 2 competition from the TSB. The key goal of the project is to identify novel IB routes to an active pharmaceutical ingredient (API) that is currently manufactured through traditional chemical manufacturing techniques. The new technology has the potential to significantly reduce manufacturing costs whilst concomitantly allowing an increased output of the API with less manufacturing equipment. Additionally, this will have the added benefits of generating a more sustainable process as it will be more energy efficient and less reliant on hydrocarbon based technologies. A successful project will allow the consortium to compete with manufacture in low-cost economies and help ensure that production of this critical API continues in the United Kingdom.

The primary objective of this project is to develop speciality recombinant enzymes for use in the manufacture of baked goods. This feasibility project focuses on the development of recombinant enzymes, which are not currently available on the market. This study will involve the cloning and expression of genes from the enzyme of interest into multiple expression hosts to identify the most suitable expression system to develop a commercially valuable process. The enzyme will be tested in baking trials trials to evaluate its performance and suitability in the process.

Biocatalysts Ltd. will undertake a project to develop a novel enzyme for production of high value speciality yeast extracts. These speciality yeast extracts are valued for their natural taste intensification properties, ability to mask undesirable bitter notes, creation of umami flavours and their use in reduced salt content food recipes.

This feasability study is designed to integrate two emerging technolgies – (1) Bioinformatics assisted design of novel enzyme characteristics, (2) Rapid in vitro screening of enzyme variants prior to expression in host microorganisms and subsequent commercial scale enzyme production. By using initial in vitro protein synthesis to test enzyme variants we will be able to initially circumvent the more usual cumbersome and time-consuming route of cloning each variant into a host organism, small-scale enzyme expression and purification and then subsequent enzyme characterisation. The success of this study will result in a novel platform for rapid commercial enzyme development that will place Biocatalysts Ltd at the cutting edge of this developmental technology.

Leukolectin is a novel, patented molecule, exhibiting (in pre-clinical tests) remarkable benefits for the treatment of a range of skin, autoimmune and gastrointestinal disorders. Leukolectin is absent in many disease states, suggesting that its presence is critical for preventing the listed ailments. By creating a range of topical and oral medicaments containing Leukolectin, Seagarden, a Norwegian company who manufacture seafood ingredients and marine bioactives, hope to dramatically improve the severity of symptoms experienced by millions of suffers around the World. The project will be facilitated by Biocatalysts Ltd, a UK enzyme developer and manufacturer, who have vast experience of large-scale manufacturing of proteins such as leukolectin. Production of leukolectin via fermentation will ensure that production costs of these medical nutrition products are kept to a minimum, and that leukolectin is produced using a sustainable and environmentally-friendly process.

This project is designed to manufacture a useful class of organic chemicals, used in paint formulations, starting with a waste by-product from the chemical industry and transforming it to the desired material by use of biocatalysis. The current chemical route employs caustic soda and sulphuric acid, and as well as producing the desired product, also co-produces a large amount of waste. The biocatalytic route is very materials-efficient and also much more energy-efficient. The project brings together the University of Northumbria, an acknowledged centre of excellence in Biotransformations, Biocatalysts Ltd, a well-established manufacturer of biocatalysts for industrial use and Chemoxy International Ltd, a medium sized UK chemical company who currently manufactures a range of eco-friendly solvents for use in surface coatings applications.

Biocatalysts Ltd will undertake a project to develop new thermolabile enzymes for production of high value food chemicals. As part of the project the company will work with the University of Swansea to use novel in silico modelling techniques to identify enzyme structures that have optimal performance with respect to both specificity and thermal lability.

Several scientific studies have demonstrated that excessive intake of sodium, which is a constituent of salt (NaCl), is considered to be a risk factor which causes significant health problems such as heart diseases (e.g. hypertension) and vascular diseases. Reduction of salt in food products represents a major technological and safety challenge to food producers. There exists a need in the food industry to provide ingredients that can enhance the salty taste of food products so that sodium usage rates can be reduced or eliminated. This feasibility study is a collaborative work between Biocatalysts Ltd and the University of Manchester. The focus is on cloning, expression and production of novel enzymes selected for their ability to produce compounds enhancing flavours in low salt food; in order to supply this enzyme to a wide range of food manufacturers in the future.

The project focuses on the production of biofuels using municipal waste (MW) which is plentiful, sustainable and environmentally friendly. The partners will develop and optimise novel and proprietary technology for 1) pre-treatment based on autoclave technology to produce an homogenous cellulosic fibre (Aerothermal), 2) enzymatic hydrolysis to release fermentable sugars (Biocatalysts) and 3) fermentation of sugars to biobutanol (Green Biologics). All three unit operations are highly innovative. In the project, we plan to perform simultaneous enzymatic hydrolysis and fermentation in a single stage coupled with autoclave pre-treatment. The evaluation of net GHG emissions savings will be performed by North Energy. These calculations form an integral part of the design and development process. The partners offer an "end to end " process solution for the producing cheap and sustainable next generation biofuels. In this project, the process will be demonstrated at pilot-scale.

The project focuses on the production of biofuels using municipal waste (MW) which is plentiful, sustainable and environmentally friendly. The partners will develop and optimise novel and proprietary technology for 1) pre-treatment based on autoclave technology to produce an homogenous cellulosic fibre (Aerothermal), 2) enzymatic hydrolysis to release fermentable sugars (Biocatalysts) and 3) fermentation of sugars to biobutanol (Green Biologics). All three unit operations are highly innovative. In the project, we plan to perform simultaneous enzymatic hydrolysis and fermentation in a single stage coupled with autoclave pre-treatment. The evaluation of net GHG emissions savings will be performed by North Energy. These calculations form an integral part of the design and development process. The partners offer an "end to end " process solution for producing cheap and sustainable next generation biofuels. In this project, the process will be demonstrated at pilot-scale.

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