Commercially successful enzymes

Glyphosate kills plants by specifically inhibiting one critical plant enzyme used in the biosynthesis of aromatic amino acids. As such, glyphosate was one of the first commercially successful herbicides to have a primary identified enzyme site of action in plants (4,5). 

Four major areas of electrochemistry related to medical diagnostics have been reviewed. Blood pH and gas measurements as well as ISE s represent relatively mature areas which enjoy widespread commercialization. New approaches should yield devices which have superior performance and which are less expensive to produce. Enzyme electrodes and electrochemical immunoassay arc still largely experimental, but the intense level of current research effort coupled with some interesting recent developments should lead to commercial success over the next decade. 

Enzymes have been proposed as a means of subtractive shrink-resist treatment. Their use has been discussed already in section 10.4-2. There are difficulties, however, in the commercially successful application of enzymes to wool at present. 

Fungal proteases have been investigated extensively in search of suitable milk clotting enzymes. Patents have been issued for production of rennets from E. parasitica, M. Pusillus var. Lindt and M. miehei var. Cooney et Emerson. These have been approved in the United States as secondary direct food additives (FDA. 1984B) and have experienced considerable commercial success in the United States as milk-clotting enzymes for cheese manufacture. Many other fungal sources have also been tried in the effort to find an inexpensive replacement for chymosin. 

Another major benefit of the purity of CLCs relates to the fact that many commercially available enzyme products actually contain more than one enzyme, and these contaminating enzymes can often lead to undesired side reactions. In the case of a resolution this can mean the difference between success and failure. For example, in the resolution of racemic ketoprofen by ester hydrolysis (Fig. 1), the enantioselectivity using crude Candida rugosa lipase is poor (E = 5). 

One of the most important problems in the development of commercial biosensors is the stabilization of the enzymes used as the biological detection agents in the sensor. Although many different biosensors have been constructed, few have been developed in commercially successful instruments. The molecular parameters which influence the activity and stability of enzymes in die dry state, and when re-hydrated in an electrode surface, have been investigated A new and novel system has been developed, which appears to have broad application to the stabilization of enzymes. The use of this system to stabilize enzymes on electrodes is reported, together with a discussion on the mode of action of stabilization in general. 

They coupled Bob Fildes DAAO-enzyme first step with an acylase-cleavage step to generate a commercially successful process for producing 7-aminocephalosporanic acid.7... 

There has been considerable growth of interest in so-called Green Chemistry or Sustainable Chemistry over the last quarter century. The terms Green and Sustainable have given new prominence to fermentation and enzyme-mediated processes and to systems that operate in water. Such processes build on the already major contribution that fermentation processes make to the pharmaceutical industry. As an aside, several important classes of API owe their commercial success to the fermentation of microorganisms ... 

Identifies properties and requirements which contribute to the commercial success or failure of a new enzyme... 

Economic Considerations. The most important consideration in determining whether an enzyme will be a commercial success is the economics of its use—will the cost of using the enzyme be at least equal to the value of the changes rendered through its use This principle has interesting ramifications that tend to horrify the classical enzyme chemist. 

Identification of Applications. Commercial success presupposes the existence of a need that could be filled by a particular enzyme. In recent years, the development of soy protein and soy products has identified the need to eliminate the flatulence factor from these products. This led to the development of the means for producing the enzyme, stacchyase, by a commercial firm. (Interestingly, this enzyme preparation is now being promoted as an a-galactosidase to break down raffinose in beet sugar syrup.) Identification of the need therefore, preceeds commercialization, even where the specific enzyme is known to exist and where its scale-up is possible. 

Enzyme sensors can measure analytes that are the substrates of enzymatic reactions. Thermometric sensors can measure the heat produced by the enzyme reaction [31], while optical or electrochemical transducers measure a product produced or cofactor consumed in the reaction. For example, several urea sensors are based on the hydrolysis of urea by urease producing ammonia, which can be detected by an ammonium ion-selective ISE or ISFET [48] or a conductometric device [49]. Amperometric enzyme sensors are based on the measurement of an electroactive product or cofactor [50] an example is the glucose oxidase-based sensor for glucose, the most commercially successful biosensor. Enzymes are incorporated in amperometric sensors in functionalised monolayers [51], entrapped in polymers [52], carbon pastes [53] or zeolites [54]. Other catalytic biological systems such as micro-organisms, abzymes, organelles and tissue slices have also been combined with electrochemical transducers. 

For commercial success, any 8-lactamase inhibitor must have the right balance of in vivo activity, stability, pharmacokinetic profile, tolerance, safety and cost-efficiency, as well as demonstrating in vitro activity against isolated enzymes and intact bacteria. To date, only clavulanic acid and sulbactam have fulfilled these stringent criteria. 

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