Enzymatic manufacture

Biocatalytic process Enzymes in production Enzymatic manufacture... 

Scheme 7. Enzymatic manufacturing process for intermediate 24. Table 1. Green chemistry metrics for scale-up of 24.

Five novel triacylglycerols (TAGs) were enzymatically manufactured to contain arachidonoyl, stearoyl, and palmitoyl substituents (e.g., triarachidonin, 1,3-diarachi-donoyl-2-stearoyl). Baseline separation was generated on two 40°C 250 x 4.6 mm C 8 columns in series (RI detector) using a 67/33 acetone/acetonitrile mobile phase. Elution was complete in <40 min [873]. 

The first, and a very important, example of the enzymatic manufacture of a bulk synthetic chemical is the biosynthesis of acrylamide from acrylonitrile (Reaction 16.11). The chemical pathway that has been used for this transformation is definitely not a green process in that it involves the... 

Enzymatic hydrolysis is also used for the preparation of L-amino acids. Racemic D- and L-amino acids and their acyl-derivatives obtained chemically can be resolved enzymatically to yield their natural L-forms. Aminoacylases such as that from Pispergillus OTj e specifically hydrolyze L-enantiomers of acyl-DL-amino acids. The resulting L-amino acid can be separated readily from the unchanged acyl-D form which is racemized and subjected to further hydrolysis. Several L-amino acids, eg, methionine [63-68-3], phenylalanine [63-91-2], tryptophan [73-22-3], and valine [72-18-4] have been manufactured by this process in Japan and production costs have been reduced by 40% through the appHcation of immobilized cell technology (75). Cyclohexane chloride, which is a by-product in nylon manufacture, is chemically converted to DL-amino-S-caprolactam [105-60-2] (23) which is resolved and/or racemized to (24)... 

Enzymatic hydrolysis of A/-acylamino acids by amino acylase and amino acid esters by Hpase or carboxy esterase (70) is one kind of kinetic resolution. Kinetic resolution is found in chemical synthesis such as by epoxidation of racemic allyl alcohol and asymmetric hydrogenation (71). New routes for amino acid manufacturing are anticipated. 

Production by Isolation. Natural cysteine and cystine have been manufactured by hydrolysis and isolation from keratin protein, eg, hair and feathers. Today the principal manufacturing of cysteine depends on enzymatic production that was developed in the 1970s (213). 

Acid-modified starches are used in the manufacture of gum candies because they form hot concentrated pastes that form strong gels on cooling. ThermaUzed starches are used in foods to bind and carry flavors and colors. Sweetening agents (com symp, HFCS) are made from starch by enzymatic or acid treatment as previously noted. 

A pilot plant ia India has been estabUshed to extract fiber, pulp, and juice from the leaves of sisal plants. The fiber is sold direcdy or used to manufacture rope, the cmshed pulp is used ia paper processiag, and the juice is an excellent source of hecogenin. During a three- to five-day fermentation of the juice, partial enzymatic hydrolysis causes hecogenin to precipitate as the hemisaponin ia the form of a fine sludge. This sediment is hydrolyzed with aqueous hydrochloric acid, neutralized, and filtered. This filter cake is washed with water and extracted with alcohol. The yield of hecogenin varies between 0.05 and 0.1% by the weight of the leaf (126). 

Process Va.ria.tlons. The conventional techniques for tea manufacture have been replaced in part by newer processing methods adopted for a greater degree of automation and control. These newer methods include withering modification (78), different types of maceration equipment (79), closed systems for fermentation (80), and fluid-bed dryers (81). A thermal process has been described which utilizes decreased time periods for enzymatic reactions but depends on heat treatment at 50—65°C to develop black tea character (82). It is claimed that tannin—protein complex formation is decreased and, therefore, greater tannin extractabiUty is achieved. Tea value is beheved to be increased through use of this process. 

The second most important group of immobilized enzymes is stiU the penicillin G and V acylases. These are used in the pharmaceutical industry to make the intermediate 6-aminopenici11anic acid [551-16-6] (6-APA), which in turn is used to manufacture semisynthetic penicillins, in particular ampicilHn [69-53-4] and amoxicillin [26787-78-0]. This is a remarkable example of how a complex chemical synthesis can be replaced with a simple enzymatic one ... 

The primary steps in the conversion of starch are Uquefaction, saccharification, and isomerization. By controlling the enzymatic reactions, sugars of different sweetness can be produced to suit the various needs of manufacturers of food and nonalcohoUc beverages. 

Fermentation An anaerobic bioprocess. An enzymatic transformation of organic substrates, especially carbohydrates, generally accompanied by the evolution of gas as a byproduct. Fermentation is used in various industrial processes for the manufacture of products (e.g., alcohols, organic acids, solvents, and cheese) by the addition of yeasts, moulds, and bacteria. 

II common protein constituent, ] -alanine, taken up... 

In section 6.6.1, we described how enzymatic methods have come to dominate the production of the important intermediates used in the manufacture of semi-synthetic -lactams. In principle, the hydrolytic penicillin acylases may be used in the reverse direction to add acyl groups to 6-APA. For example, a two-step enzymatic process has been described for the preparation of ampiciilin (D-(-)-a-aminobenzylpenidllin structure shown in Figure 6.17). 

Catalytic transformations can be divided on the basis of the catalyst-type - homogeneous, heterogeneous or enzymatic - or the type of conversion. We have opted for a compromise a division based partly on type of conversion (reduction, oxidation and C-C bond formation, and partly on catalyst type (solid acids and bases, and biocatalysts). Finally, enantioselective catalysis is a recurring theme in fine chemicals manufacture, e.g. in the production of pharmaceutical intermediates, and a separate section is devoted to this topic. 

Some companies are successfully integrating chemo- and biocatalytic transformations in multi-step syntheses. An elegant example is the Lonza nicotinamide process mentioned earlier (.see Fig. 2.34). The raw material, 2-methylpentane-1,5-diamine, is produced by hydrogenation of 2-methylglutaronitrile, a byproduct of the manufacture of nylon-6,6 intermediates by hydrocyanation of butadiene. The process involves a zeolite-catalysed cyciization in the vapour phase, followed by palladium-catalysed dehydrogenation, vapour-pha.se ammoxidation with NH3/O2 over an oxide catalyst, and, finally, enzymatic hydrolysis of a nitrile to an amide. 

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