Flow biotransformation reactions

Hydrolases — especially lipases — proved to be versatile biocatalysts for synthetic biotransformations [79, 80). The vast majority of the enzymatic stereoselective processes have been performed so far in batch mode [29, 30, 81]. Very recently, a review appeared on lipase-catalyzed reactions under continuous-flow conditions [82], and here we extend this overview with an analysis of the range of selectivities, effects of reaction conditions and the mode of enzyme immobilization on the lipase, and in general hydrolase-catalyzed continuous-flow biotransformations. 

Solid-supported enzymes for use in batch reactions are well-known, and the exploitation of biotransformation reactions under flow conditions has been the focus of much research. Herein, only a few representative examples of enzymatic catalysis in microreactors are described [168-171]. 

Often, PBPK models for toxicokinetics application require special considerations (e.g., volatile toxicants may incur tissue-air partition coefficients and alveolar elimination rates). Partition coefficients are generally obtained by measurement in the laboratory, tissue volume/blood flow data are mostly available from the scientific literature (with allometric scaling from species to species), and biotransformation data are usually obtained from in vivo and in vitro kinetic studies. Biochemical constants for metabolic pathways are captured using the maximum rate of reaction, or Vmax5 and the binding affinity of the particular substrate for the metabolizing enzyme. 

PROBABLE FATE photolysis, photooxidation to chlorinated biphenyls and benzophe-nones probable, indirect photolysis may be significant based on the behavior of the related compound DDT, direct photolysis half-life in water >150 yrs, photooxidation half-life in air 13.3-133 hrs oxidation, not an important process, vapor phase half-life in the atmosphere 1.71 days from reaction with photochemically produced hydroxyl radicals hydrolysis, not an important process, will not hydrolyze in soil volatilization expected to be an important process, evaporation half-life 1.82 days from a river 1 m deep, flowing at Im/sec with a wind velocity of 3 m/sec sorption is an important process, expected to adsorb to sediment if released to water biological processes biotransformation and bioaccumulation are important processes biodegradation expected to be slow... 

At the same time, engineering rules that apply to whole-cell redox reactions have to be taken into account. In general, aeration and/or carbon dioxide production is involved, and plug flow reactors are not appropriate. Moreover, oxygen transfer to immobilized cells is not very efficient. Consequently, continuous reactors are not very suitable for redox biotransformations with whole cells [12]. These biotransformations can best be carried out in (fed) batch reactors with free cells. Since the production of the cells will also involve a (fed) batch process, these processes may easily be combined. Then, the cells are produced in a fed-batch fer-... 

A typical process flow diagram for the production of chiral amines using aminotransferases is shown in Figure 7.8. The buffering agent, pyridoxal 5-phosphate, amine donor, enzyme, and substrate ketone in aqueous solution are mixed in a biotransformation vessel. The desired reaction conditions such as temperature, pH, amine donor, and acceptor concentrations are maintained during transamination reaction. The transamination reaction time depends on the rate at which transaminase is catalyzing the reaction, while the extent of conversion depends on... 

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