A small-footprint reactor for biosynthesis and seperation of industrial chemicals

The primary objective of the project is the novel combination of the Counter Current Chromatography (CCC) developed by the Brunel Institute for Bioengineering (BIB), used to separate biomolecules, with industrially relevant biocatalysts developed by Ingenza, to develop new equipment to make and isolate a range of important compounds required by industry more rapidly and efficiently than before. The success of this project will establish a new, adaptable approach to achieve highly competitive economics for UK industrial bioprocesses using low capital, small footprint, and versatile equipment with minimal waste generation compared to conventional manufacturing practices. Chromatography is a means of separating components of a mixture based on their differing affinities for the mobile and stationary liquid phases held in a column. In CCC, centrifugal force is used to hold one phase stationary in a tube and permit the mobile phase to flow over it. BIB are world leaders in making and using these CCC-centrifuges and the scale up of separations made on their small, lab machines, to larger production scale ones. Biotransformation is the process of transforming one molecule (the substrate) into another (the product) by means of a biocatalyst (an enzyme) suspended in a solvent (usually water). Ingenza have developed catalysts that aid the conversion of readily available, cheap starting materials to high value products, required by industry as starting material for a range of applications, typically carried out in bioreactors. They are particularly skilled at producing enzymes to use as natural chiral reagents to product chiral compounds. Chiral compounds have different left-handed and right-handed forms and frequently only one form is active biologically. A major driver for chiral pure drugs (i.e. only one chiral form present) is legislation by bodies that regulate new drugs (e.g FDA in USA). It can be difficult/costly to make drugs and then separate the chiral form required. It is better to use chiral reagents (such as enzyme catalysts) to make only the chiral form needed, as Ingenza do. The proposed research will establish a number of industrially important biotransformations in equipment originally developed for CCC. Preliminary investigative studies have already been undertaken by BIB/Ingenza strongly suggesting that this CCC equipment appears to be superior to existing bioreactors by virtue of its ability to remove the product of the biotransformation selectively and continuously in the mobile phase (because of CCC being a chromatographic separation process) from the starting material and biocatalyst, which can be kept in the stationary phase. This drives the reaction more quickly and efficiently towards completion. As it is a rapid and continuous process, large scale manufacture can be achieved with a relatively small machine (small footprint), a feature with economic benefits to industry. Ingenza will make a number of catalysts with which BIB will optimise the CCC as a reactor. This information will then be used by Ingenza and BIB to improve the design of the catalysts and operation of the CCC, leading to a fully optimised and cost validated small footprint reactor/separator. This reactor provides a number of benefits: i) A low-cost, generic tool to be used by researchers more easily than current methods to determine the true industrial manufacturung potential of a given enzyme ii)To provide products for life sciences companies making pharmaceuticals, nutraceuticals, food, flavours and fragrances, agrochemicals eg chiral amines and unnatural amino acids (produced by Ingenza enzymes) are two of the largest classes of chiral intermediates needed by industry. iii) Cost effective manufactures iv) Environmentally friendly ( Green ) low energy requiring synthesis of a range of products, using renewable resources, minimal waste and solvent usage,thus replacing solvent wasteful chemical processes