Biochemical process industry

Bioreactors are the core of bioprocesses, as they provide the key link between the initial feedstock and the product, where chemical modifications are carried out. Vessels used as bioreactors have to be designed and operated in such a manner to accommodate the requirements of a given type of cells or enzymes to perform in conditions that maximize productivity. Therefore, bioreactor engineering is a cross-disciplinary area, where biology and engineering interact closely. Key issues for bioreactor design and operation are addressed and illustrated by some examples that highlight the relevance of biochemical process industry. 

The engineer s contribution to the development of the penicillin fermentation was a very important one. The outgrowth of the undertaking was the pure-culture technique, carried out in aerated and agitated deep-tank fer-mentors. This technique, similar to its antecedent used for yeast propagation, introduced to the biochemical process industry refined fermentation equipment capable of being maintained under aseptic conditions even when vigorously aerated. The technique has now been applied widely with minor modifications to the production of other antibiotics, amino acids, steroids, enzymes, and therapeutic proteins. 

Isolation procedures for many biochemicals are based on chromatography. Practically any substance can be selected from a crude mixture and eluted at relatively high purity from a chromatographic column with the right combination of adsorbent, conditions, and eluant. For bench scale or for a small pilot plant, such chromatography has rendered alternate procedures such as electrophoresis nearly obsolete. Unfortunately, as size increases, dispersion in the column ruins resolution. To produce small amounts or up to tens of kilograms per year, chromatography is an excellent choice. When the scale-up problem is solved, these procedures should displace some of the conventional steps in the chemical process industries. 

At present most bioprocesses in the organic chemical industry are actually mixed chemical/biochemical processes. In such processes, chemically synthesised educts (chemical precursors) are biotransformed and then re-enter chemical synthesis. The main reason for this approach is that, in general, higher volumetric productivities can be achieved with chemical catalysts. 

The immobilisation of proteins into inorganic mesoporous host materials has attracted considerable attention due to the potential applications in biochemical, biomedical, industrial and bio-analytical fields [1] Biocompatible supports endowed with fluorescent tracers and adequately modified for specific interactions with cellular antigens are an amenable tool for image in living cells processes that are relevant to diseases. 

Although the general principles of separation processes are applicable widely across the process industries, more specialised techniques are now being developed. Reference is made in Chapter 13 to the use of supercritical fluids, such as carbon dioxide, for the extraction of components from naturally produced materials in the food industry, and to the applications of aqueous two-phase systems of low interfacial tensions for the separation of the products from bioreactors, many of which will be degraded by the action of harsh organic solvents. In many cases, biochemical separations may involve separation processes of up to ten stages, possibly with each utilising a different technique. Very often, differences in both physical and chemical properties are utilised. Frequently... 

Metabolites are generated by the body s own biochemical processes as a way to facilitate excretion of xenobiotics. The enzymes catalysing in vivo modification of drugs and druglike molecules have a fundamental significance for the pharmaceutical industry. This was once primarily the field of the pharmacologist, but interest in metabolic reactions... 

Another important advance adding to the value of PBPK modeling in the pharmaceutical industry are physiological, mechanistic models developed to describe oral absorption in humans and preclinical species. Oral absorption is a complex process determined by the interplay of physiological and biochemical processes, physicochemical properties of the compound and formulation factors. Physiologically based models to predict oral absorption in animals and humans have recently been reviewed [18, 19] and several models are now commercially available. The commercial models have not been published in detail because of proprietary reasons but in essence they are transit models segmenting the gastrointestinal tract... 

Oxidation of carbohydrates can be achieved by either chemical or biochemical processes [98, 99]. Owing to their cation sequestering properties, the resulting carboxylic derivatives find potential applications in the detergent industries [100, 101]. Although homogeneous catalysts are often used in oxidation processes, utilization of solid catalysts has proved to be a feasible alternative [102]. 

Previous chapters in this volume have been concerned with chemical reaction engineering and refer to reactions typical of those commonplace in the chemical process industries. There is another class of reactions, often not thought of as being widely employed in industrial processes, but which are finding increasing application, particularly in the production of fine chemicals. These are biochemical reactions, which are characterised by their use of enzymes or whole cells (mainly micro-organisms) to carry out specific conversions. The exploitation of such reactions by man is by no means a recent development—the fermentation of fruit juices to make alcohol and its subsequent oxidation to vinegar are both examples of biochemical reactions which have been used since antiquity. 

These sources of multiplicity are very frequent in actual chemical/biological processes. Chapter 7 highlights examples of multiplicity, bifurcation, and chaotic behavior for a number of experimental and industrial chemical/biochemical processes. We also include Appendix 2 on multiplicity and bifurcation at the end of the book. 

---