Downstream Processing Schemes

Marty et al. have reported a complete pilot-plant reactor/separator system for carrying out enzymatic reactions in SCFs. The plant comprises a continuously operated tubular reaction vessel followed by four cyclone separators. The separators may be put in descending pressure order by adjusting needle valves between each vessel. Liquid products are recovered from the bottom of each vessel discontinuously [15]. 

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Fig. 17.1. Conventional downstream processing scheme for the purification of proteins.

By reducing the solvent-power of a dense gas in several stages, fractionation of the product and unreacted reactants is possible. Fractionation is also possible by extracting the mixture, usually with the same dense gas as used in reaction, but under different process conditions. In all downstream processing schemes, various particle-formation techniques [31] or chromatographic techniques can be integrated. 

Figure 4.9-6 Downstream processing schemes for enzymatically catalyzed reactions using SCFs as solvents for reaction and purification.

Downstream Processing. In addition to extraction, various downstream operations are often carried out on the BTX product to produce products in proportions to fit the market demand. A typical aromatics processing scheme is shown in Eigure 8 in which ben2ene, xylene, and o-xylene are the products. 

FIG. 22-86 Process scheme for protein extraction in aqueous two-phase systems for the downstream processing of intracellular proteins, incorporating PEG and salt recycling. RepHnted from Kelly and Hatton in Stephanopoulos (ed), op. cit. adapted from Qre-oe and Kula, op. cit.]... 

The Alphabutol process (Figure 7-8) operates at low temperatures (50-55°C) and relatively low pressures (22-27 atm). The reaction occurs in the liquid phase without a solvent. The process scheme includes four sections the reactor, the co-catalyst injection, catalyst removal, and distillation. The continuous co-catalyst injection of an organo-hasic compound deactivates the catalyst downstream of the reactor withdrawal valve to limit isomerization of 1-hutene to 2-hutene. Table 7-2 shows the feed and product quality from the dimerization process. 

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. 

Most of the toluene and xylenes have their origin in catalytic reforming or olefins plants. From there, the processing schemes vary widely from site to site. The schematic in Figure 3-6 captures most of the variations, although its hard to portray that some plants separate the BTXs from each other early in the scheme while others do it at varying places downstream of an aromatics recovery unit. 

The separation schemes vary with the state of the products. For example, intracellular products must first be released by disrupting the cells, while those products bound to cell membranes must be solubilized. As the concentrations of products secreted into the fermentation media are generally very low, the recovery and concentration of such products from dilute media represent the most important steps in downstream processing. In this chapter, several cell-liquid separation methods and cell disruption techniques are discussed. 

Although the utility of transaminases has been widely examined, one such limitation is the fact that the equilibrium constant for the reaction is near unity. Therefore, a shift in this equilibrium is necessary for the reaction to be synthetically useful. A number of approaches to shift the equilibrium can be found in the literature.53 124135 Another method to shift the equilibrium is a modification of that previously described. Aspartate, when used as the amino donor, is converted into oxaloacetate (32) (Scheme 19.21). Because 32 is unstable, it decomposes to pyruvate (33) and thus favors product formation. However, because pyruvate is itself an a-keto acid, it must be removed, or it will serve as a substrate and be transaminated into alanine, which could potentially cause downstream processing problems. This is accomplished by including the alsS gene encoding for the enzyme acetolactate synthase (E.C. 4.1.3.18), which condenses two moles of pyruvate to form (S)-aceto-lactate (34). The (S)-acetolactate undergoes decarboxylation either spontaneously or by the enzyme acetolactate decarboxylase (E.C. 4.1.1.5) to the final by-product, UU-acetoin (35), which is meta-bolically inert. This process, for example, can be used for the production of both l- and d-2-aminobutyrate (36 and 37, respectively) (Scheme 19.21).8132 136 137... 

However, design constraints may limit our ability to exercise this strategy concerning fresh reactant makeup, An upstream process may establish the reactant feed flow sent to the plant. A downstream process may require on-demand production, which fixes the product flowrate from the plant. In these cases, the development of the control strategy becomes more complex because we must somehow adjust the setpoint of the dominant variable on the basis of the production rate that has been specified externally. We must balance production rate with what has been specified externally. This cannot be done in an open-loop sense, Feedback of information about actual internal plant conditions is required to determine the accumulation or depletion of the reactant components. This concept was nicely illustrated by the control strategy in Fig. 2.16, In that scheme we fixed externally the flow of fresh reactant A feed. Also, we used reactor residence time (via the effluent flowrate)... 

A dual-solvent fractional extraction process can provide a powerful separation scheme, as indicated by the examples given above, and some authors suggest that fractional extraction is not utilized as much as it could be. In many cases, instead of using full fractional extraction, standard extraction is used to recover solute from a crude feed and if the solvent-to-feed ratio is less than 1.0, concentrate the solute in a smaller solutebearing stream. Another operation such as crystallization, adsorption, or process chromatography is then used downstream for solute purification. Perhaps fractional extraction schemes should be evaluated more often as an alternative processing scheme that may have advantages. 

As an alternative, N2O can be recovered from the off-gas in pure form, either for selling or for use as an oxidant in some downstream processes. Within this context, an innovative solution has been developed by Solutia, together with the Boreskov Institute of Catalysis, in which N2O is the oxidant used for the hydroxylation of benzene to phenol in the presence ofaZSM-5 catalyst exchanged with Fe(III) [11]. Phenol can then be hydrogenated to yield cyclohexanol, hence completing the N2O cycle (Scheme 7.3). 

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