High-volumetric productivity

Continuous Stirred Tanks with Biomass Recycle. When the desired product is excreted, closing the system with respect to biomass offers a substantial reduction in the cost of nutrients. The idea is to force the cells into a sustained stationary or maintenance period where there is relatively little substrate used to grow biomass and where production of the desired product is maximized. One approach is to withhold some key nutrient so that cell growth is restricted, but to supply a carbon source and other components needed for the desired product. It is sometimes possible to maintain this state for weeks or months and to achieve high-volumetric productivities. There will be spontaneous cell loss (i.e., kd > 0), and true steady-state operation requires continuous purging and makeup. The purge can be achieved by incomplete separation and recycle... 

Cultor Ltd. (Finland) and Tuchenhagen(Germany) have developed a process, where yeast cells are adsorbed on the surface of the carrier developed for glucose isomerase (Spezyme, Table 6.1). The high volumetric productivity of the immobilized yeast cells make a conversion of dr-acetolactate to acetoin possible with only a few hours residence time in the packed bed columns. 

Reaction engineering helps in characterization and application of chemical and biological catalysts. Both types of catalyst can be retained in membrane reactors, resulting in a significant reduction of the product-specific catalyst consumption. The application of membrane reactors allows the use of non-immobilized biocatalysts with high volumetric productivities. Biocatalysts can also be immobilized in the aqueous phase of an aqueous-organic two-phase system. Here the choice of the enzyme-solvent combination and the process parameters are crucial for a successful application. 

The question of high volumetric productivity is coupled to the solubility of substrates. High space-time-yields have been demonstrated to be correlated with high solubilities of substrates (Bommarius, 2001). 

One of the most important goals is the enhancement of volumetric productivities. As high volumetric productivity correlates with high solubility of substrates (Chapter 2 Bommarius, 2001), enhancement of substrate solubility is an excellent measure for improving volumetric productivity. 

For most enzymes, the CLEC is much more robust than the simple isolated enzyme. CLECs can withstand higher temperatures, they denature more slowly in organic solvents, and they are less susceptible to proteolysis [71]. Moreover, since there is no external support involved, CLECs exhibit a high volumetric productivity. These advantages, together with the tunable particle size (typically 1-100 pm), make CLECs attractive for industrial biocatalysis applications. 

More examples for applied organocatalysis are presented by H. Groger, who gives an overview of organocatalytic methods already applied on a technical scale. Based on case studies, he shows several examples that satisfy the criteria of a technically feasible process such as high catalyst activity and stability, economic access, sustainability, atom economy, and high volumetric productivity. 

Figure 9-23 Impinging jet crystallization has very high volumetric productivity.

The first generation process developed for the production of L-carnitine was a single-stage continuous process with cell-recycling that utilized the maintenance phase production that is characteristic of this strain. This process had a very high volumetric productivity of 130 g/L/d in the steady state [3], Owing to the kinetics of this process the product solution contained 92% L-carnitine and 8% unconverted butyrobetaine. L-Carnitine and butyrobetaine have very similar physio-chemical properties, which makes their separation from the product solution diffi-... 

A further industrially important lyase for the production of L-amino acids is the tyrosine phenol lyase [39]. This biocatalyst is used by Ajinomoto in the production of the pharmaceutically important L-3,4-dihydroxyphenylalanine (L-dopa), 32, which is applied in the treatment of Parkinson s disease. The reaction concept is based on a one-pot three-component synthesis starting from catechol, 30, pyruvic acid, 31, and ammonia in the presence of suspended whole cells (strain Erwinia herbicola) containing the tyrosine phenol lyase biocatalyst (Fig. 16). A key feature of this process is the high volumetric productivity of 110 g/L of the desired L-dopa product. Notably, this reaction runs with an annual capacity of 250 tons. 

The specific production profile (qAb) of the cells was stable for the majority of the process, with an average of 15 pg per cell per day. Higher values at the end of the process were due to cell retention device failure. High volumetric production rates (VPR) were achieved during this process, with an average VPR of 0.76 g per day calculated over the entire process, 0.9 g per day at approximately 80 x 10 mL and an upper VPR of 3 g per day achieved at 150 x 10 mL . ... 

L/[min (kg DM)] humidity of inlet air, 95% outside fermenter temperature, 29°C and moisture content of the solid substrate 80% (Nwe and Stevens 2006 cited in [8]). The SSF offers numerous advantages over SMF. These include high volumetric productivity, relatively higher concentration of the products, less effluent generation, and simple fermentation equipment, etc. [15]. 

The primary objective functions for production of metabolites are to maximize the concentration (to minimize recovery costs) while maintaining high conversion yields of costly raw materials to the product, under conditions of high volumetric productivity (to reduce capital cost). The usual approach is to rapidly produce a high cell concentration under conditions that maximize the conversion rate of raw materials to the desired product. 

Among the advantages of perfusion reactors (21) are (1) high volumetric productivity (2) partial purification of the product by removal of cell debris and inhibitory byproducts, as well as enzymes (released by dead cells) that may destroy desirable products (3) imposition of limits on the amount of time that metabolic products are exposed to potentially harmful processing conditions and (4) facilitation of process control via ease of regulation and maintenance of the environments of the cells. 

During the past decades, photobioreactors have found promising apphcations, in particular for high-value products, for example, in pharmacy, cosmetics, and aquaculture feeds. Nevertheless, the development of industrial photobioreactors stiU requires optimization efforts, especially for achieving a high volumetric production rate in the context of large-scale... 

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