Productivity volumetric

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 system works even at 3 M substrate concentration with 90% conversion, 98.5%ee, and essentially no substrate inhibition. Volumetric productivity, which is of great importance in any industrial application, was enhanced by the process of directed evolution [20]. 

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... 

Using the optimum settings, biodiesel is produced at a volumetric production rate of 61 kg biodiesel/m -min, which compares well with 42 kg/m -min reported for typical batch processes (17). In addition, the current process is much more efficient since there is no separate separation step and reactor cleaning in between batches can be omitted (18). 

With the reaction performance improved, attention turned to isolation of 3. The work-up of this reaction was complicated by the solubility of TH F in water and the low solubility of 3 in most organic solvents. Using extraction to remove residual magnesium salts would have severely limited volumetric productivity. We found that 3 could be isolated by quenching the reaction into aqueous HC1. Crude 3 was isolated after concentrating the organic layer. Residual TH F and magnesium salts were then removed by recrystallization from AcOH/water with less than 1% loss of 3. 

At low temperatures, the nonenzymatic reaction is reduced to a larger extent than the enzymatic reaction. The mass transfer rate is reduced to a smaller extent. Mass transfer limitation is required for high enantiomeric excess and determines the conversion rate. Therefore, the volumetric productivity decreases at lower temperatures. The equilibrium constant is considerably higher at low temperatures, resulting in a higher extent of conversion or a lower HCN requirement. Both the volumetric productivity and the required enzyme concentration increase by increasing the reaction temperature and aqueous-phase volume while meeting the required conversion and enantiomeric excess [44]. The influence of the reaction medium (solvent and water activity) is much more difficult to rationalize and predict [45],... 

Numerous biocatalytic routes to this challenging intermediate have been reported. " For example. Fox et al. have recently developed an efficient regioselective cyanation starting from low-cost epichlorohydrin (Scheme 1.26). Initial experiments found that halohydrin dehydrogenase from Agrobacterium radiobacter expressed in E. coli produced the desired product, but inefficiently. To meet the projected cost requirements for economic viability, the product needed to be produced at 100 g L with complete conversion and a 4000-fold increase in volumetric productivity. The biocatalyst needed to function under neutral conditions to avoid by-product formation, which causes downstream processing issues. 

The volumetric production rate of species k due to electrochemical reaction occurring at the triple-phase boundary is given by Faraday s law... 

A major objective of fermentation in research industry is to maximize the volumetric productivity to obtain the highest possible amount of product in a given volume within in a certain time. The main problems arising from HCDC are limitation and/or inhibition of substrates with respect to growth, accumulation of products or metabolic by-products to a growth-inhibitory level, a high... 

Suspension systems can be operated in different modes batch, fed-batch, chemostat, and perfusion (Fig. 1). These operation modes differ basically in the way nutrient supply and metabolite removal are accomplished, which in turn determines cell concentration, product titer and volumetric productivity that can be achieved [8]. The intrinsic limitation of batch processes, where cells are exposed to a constantly changing environment, limits full expression of growth and metabolic potentials. This aspect is partially overcome in fed-batch cultures, where a special feeding strategy prolonges the culture and allows an increase in cell concentration to be achieved. In perfusion and chemostat processes nutrients are continuously fed to the bioreactor, while the same amount of spent medium is withdrawn. However, in perfusion cultures the cells are retained within the bioreactor, as opposed to continuous-flow culture (chemostat), which washes cells out with the withdrawn medium [9]. 

Volumetric productivity is a good performance index in what concerns the optimization of bioreactor operation. It can be used in process improvement at a defined scale and also for process scale-up, since it is a dimensionless variable. Therefore bioreactor operation and scale-up for CLP and VLP production will be addressed as the identification of the operational conditions that result in the best volumetric productivity. 

Chemical reactions enhanced by catalysts or enzymes are an integral part of the manufacturing processes for the majority of chemical products. The total market for catalysts and enzymes amounts to 11.5 billion (2005), of which catalysts account for about 80%. It consists of four main applications environment (e.g., automotive catalysts), 31% polymers (e.g., polyethylene and polypropylene), 24% petroleum processing (e.g., cracking and reforming), 23% and chemicals, 22%. Within the latter, particularly the catalysts and enzymes for chiral synthesis are noteworthy. Within catalysts, BINAPs [i.e., derivatives of 2,2 -bis(diphenylphosphino) -1, l -bis-l,l -binaphthyl) have made a great foray into chiral synthesis. Within enzymes, apart from bread-and-butter products, like lipases, nitrilases, acylases, lactamases, and esterases, there are products tailored for specific processes. These specialty enzymes improve the volumetric productivity 100-fold and more. Fine-chemical companies, which have an important captive use of enzymes, are offering them to third parties. Two examples are described here ... 

Cabral and coworkers [253] have investigated the batch mode synthesis of a dipeptide acetyl phenylalanine leucinamide (AcPhe-Leu-NH2) catalyzed by a-chymotrypsin in a ceramic ultrafiltration membrane reactor using a TTAB/oc-tanol/heptane reverse micellar system. Separation of the dipeptide was achieved by selective precipitation. Later on the same group successfully synthesized the same dipeptide in the same reactor system in a continuous mode [254] with high yields (70-80%) and recovery (75-90%). The volumetric production was as high as 4.3 mmol peptide/l/day with a purity of 92%. The reactor was operated for seven days continuously without any loss of enzyme activity. Hakoda et al. [255] proposed an electro-ultrafiltration bioreactor for separation of RMs containing enzyme from the product stream. A ceramic membrane module was used to separate AOT-RMs containing lipase from isooctane. Application of an electric field enhanced the ultrafiltration efficiency (flux) and it further improved when the anode and cathode were placed in the permeate and the reten-tate side respectively. 

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. 

Overall volumetric productivity Qp (mol.m s ) (it is also common to use a yearly basis) is the average production capacity per unit volume and time of the bioreactor. The overall volumetric productivity is confined, on the one hand, by physical constraints, such as mass and heat transfer, and, on the other hand, by biocatalyst concentration... 

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