Bioprocesses Bioprocessing cost

De Palma A. Downstream processing operations hold the key to bioprocess cost control. Gen Eng News 1996 19 19-20. 

Industrial processes cmivert low-value carbon into high value-added products. To be economically viable, the cost of the overall bioprocess must be significantly less than the selling price of the product. Many variables contribute to bioprocess costs, but for bulk biochemicals such as biofuels and industrial chemicals (which many isoprenoids are used for), the price of the feedstock is the primary cost driver (Rude and Schirmer 2009 WUlke and Vorlop 2008). Currently, carbohydrates from plant biomass are the most important carbon feedstock for fermentation. Plants accumulate simple sugars, cellulose or lipids, which bacteria can convert into energy, biomass and products. Popular model organisms exploited in industry (such as... 

Significant additional progress will be necessary before cost-effective production of vitamin B by bioprocesses is possible. 

A number of the genes involved in the biosynthesis of thiamine in E. coli (89—92), i hium meliloti (93), B. suhtilis (94), and Schi saccharomycespomhe (95,96) have been mapped, cloned, sequenced, and associated with biosynthetic functions. Thiamine biosynthesis is tightly controlled by feedback and repression mechanisms limiting overproduction (97,98). A cost-effective bioprocess for production of thiamine will require significant additional progress. 

Bioprocess Control An industrial fermenter is a fairly sophisticated device with control of temperature, aeration rate, and perhaps pH, concentration of dissolved oxygen, or some nutrient concentration. There has been a strong trend to automated data collection and analysis. Analog control is stiU very common, but when a computer is available for on-line data collec tion, it makes sense to use it for control as well. More elaborate measurements are performed with research bioreactors, but each new electrode or assay adds more work, additional costs, and potential headaches. Most of the functional relationships in biotechnology are nonlinear, but this may not hinder control when bioprocess operate over a narrow range of conditions. Furthermore, process control is far advanced beyond the days when the main tools for designing control systems were intended for linear systems. 

Costs of downstream processing for bioprocesses are increased by 1) low concentrations of products, 2) numerous impurities at low concentration and 3) intracellular materials (if cell disruption is necessary). However, the high specificity of biocatalysts is a benefit to downstream processing since products closely related to the desired product are less likely to be present Waste products of bioprocesses are likely to be less environmentally damaging, which also reduces downstream processing costs. 

There are several methods to monitor the off-gas analysis. Online gas chromatography is commonly used. The daily operation for inlet and outlet gases is balanced to project growth in the bioprocess. High operating cost is the disadvantage of the online system. 

Process economics for biological products was discussed by Harrison et al. (op. cit., pp. 334—369) and Datar and Rosen [in Asenjo (ed.). Separation Processes in Biotechnology, DeUcer, New York, 1990, pp. 741-793] at length, and also by Ladisch (op. cit., pp. 401—430). They provided some illustrative examples with cost an yses. Bioprocess design software can also prove helpful in the overall design process (Harrison et al., op. cit., pp. 343-369). 

Before the details of a particular reactor are specified, the biochemical engineer must develop a process strategy that suits the biokinetic requirements of the particular organisms in use and that integrates the bioreactor into the entire process. Reactor costs, raw material costs, downstream processing requirements, and the need for auxiliary equipment will all influence the final process design. A complete discussion of this topic is beyond the scope of this chapter, but a few comments on reactor choice for particular bioprocesses is appropriate. 

In this review, we focus on the use of plant tissue culture to produce foreign proteins that have direct commercial or medical applications. The development of large-scale plant tissue culture systems for the production of biopharmaceutical proteins requires efficient, high-level expression of stable, biologically active products. To minimize the cost of protein recovery and purification, it is preferable that the expression system releases the product in a form that can be harvested from the culture medium. In addition, the relevant bioprocessing issues associated with bioreactor culture of plant cells and tissues must be addressed. 

In many practical applications, the measurement devices cover a specific range of operation, which may be used in the input or in the output of the bioprocess but not in both places. Input concentrations are usually higher than the output concentrations and thus they require two different sensors with different sensitivities which may cause an additional cost of measuring devices. This remark prevents the use of a single sensor that must be placed at the influent stream to measure a certain variable and the placed it at the output to record some ather variable or magnitud ... 

Another advantage to the incorporation of bioprocessing aids into the Step I procedure is that the clarified extract can be used directly for subsequent purification steps even without the use of a Step II system to dewater or concentrate the process stream. These factors are especidly relevant when HPLC systems arc used in Step IB for the chromatographic procedures. Nucleic acids, pigmented organics and especially cellular debris can very quickly foul an HPLC column. This is an even more important consideration for large scale protein purification schemes where the volumes of material and costs of the operation are greatly increased (3). 

Easy Cell Harvest. In this type of bioprocess the cells are the products so a method for an easy cell harvest must be provided. Neither a substantial loss in cell number nor damage to the cells is acceptable, because this would directly affect the therapeutic value of the transplant. A large number of labor-intensive isolation and purification steps is also unacceptable. This is not only because of the increase in time and costs, but also due to the increasing risk of contamination. 

The third major Hmitation of bioprocesses is the quite low product concentration compared with chemical processes, resulting in high downstream processing costs. This is mainly caused by product inhibition of cell growth and biosynthesis. Physiological improvements in cell growth and product formation only have a limited impact on this aspect. Chemical or directed mutagenesis may provide better chances for improvement. Unfortunately, the molecular mechanisms of product inhibition are not well understood. 

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