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Industrial Enzyme Classes. Commodity enzymesHigh volume (tonnes p.a)Low purity (but not necessarily so)Low cost (e.g. $5-40 per kg)Low profit marginsSpeciality enzymesLow volume (g
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1. BTY323 Lectures 15, 16Enzymes in Industry Markets
Types
Scale
Values
Future
Examples
2. Industrial Enzyme Classes Commodity enzymes
High volume (tonnes p.a)
Low purity (but not necessarily so)
Low cost (e.g. $5-40 per kg)
Low profit margins
Speciality enzymes
Low volume (g – kg)
High purity
High cost ($5 – 10,000 per g)
High profit margins
3. Enzymes in Industry Distribution of enzymes by substrate
Protein hydrolysing 59%
Carbohydrate hydrolysing 28%
Lipid hydrolysing 3%
Speciality (analytical, pharma, research) 10%
4. Enzymes in Industry
5. Industrial enzymes: Market trends Increasing 10-15% annually by volume
Increasing 4-5% annually by value
Decreased margins for commodity enzymes
Increased use of speciality enzymes
Diagnostic enzymes
Fine chemicals manufacture
Chiral separation
6. Industrial enzymes Food processing
Textiles
Grain processing
Amylases in bread-making
Lipases in flavour development
Proteases in cheese making
Pectinases in clarifying fruit juices
Cellulases in treating denim to generate ‘stone-washed’ texture/appearance
Conversion of corn starch to high fructose syrups
7. Industrial enzymes Feed enzymes
Waste management
Diagnostic enzymes Enzymes to assist in the digestibility of animal feeds (cellulase, xylanase, phytase)
Lipases as drain-cleaning agents
Reporter enzymes (alkaline phosphatase, glucose oxidase, b-glucosidase) and diagnostic enzymes (DNA polymerase)
8. Industrial enzymes Speciality Biotransformations
Lipases, esterases and oxidoreductases for chiral separations
Glucotransferases in synthesis of oligosaccharides
Thermolysin in aspartame synthesis
Nitrile hydratases in acrylamide and nicotinamide synthesis
Proteases in peptide synthesis
Penicillin acylase for manufacture of semisynthetic penicillins
Aspartase in the manufacture of L-aspartate
9. Examples of Industrial Enzyme Processes
Starch conversions and the production of High Fructose Syrups
Aspartame biosynthesis
Nitrile conversions
Acrylamide
Nicotinamide
10. Corn starch processing 1
11. Corn starch processing 2.
12. Enzyme step 1: Action of Termamyl® on starch granules Termamyl® is an a-amylase (cleaves a-1-4 glucosidic bonds in starch)
High temperature expands starch granules, making amylose and amylopectin chains more accessible
Termamyl is sufficiently stable at high temperatures if short reaction times are used
Starch hydrolysis is a batch process (the enzyme is not reused!)
13. Enzyme step 2: Conversion of maltose to glucose Amyloglucosidase is not as thermostable as Termamyl (temperature must be reduced)
Amyloglucosidase has a pH optimum of 6.5 (Termamyl® operates optimally at 8.5): pH must be reduced
Reaction kinetics are slower
Long incubations result in caramelisation of the saccharides - resulting in product loss and increase in impurities
14. Enzyme step 3: Conversion of glucose to fructose Fructose is much sweeter than glucose; it can be used as a sweetening agent in foodstuffs, and is more profitable than glucose
The enzyme xylose isomerase will convert glucose to fructose, in an equilibrium reaction
Glucose ? Fructose
A 50:50 mixture of glucose:fructose is sold as high fructose syrup (HFS)
Xylose (glucose) isomerase is much less thermostable, and inhibited by Ca ions.
15. Aspartame biosynthesis
16. Key process characteristics Immobilised enzyme allows continuous process and enzyme reuse
Proteases normally hydrolyse peptide bonds: a low water activity solvent system (organic solvent based) is necessary to reverse the normal equilibrium
Organic solvents often promote enzyme denaturation: Thermolysin® as a stable thermophilic protease
Product recovery is easy – the CBZ-L-Phe-L-Asp-OMe intermediate crystallizes out in the reaction media
17. Column-based biosynthesis of Aspartame® Thermolysin® is used in a column format
Reaction will be run continuously until substrate ‘breakthrough’ is observed
This indicates that the enzyme efficiency is dropping (inhibition or denaturation)
Several columns may be operated in series to achieve maximum conversion efficiencies
18. Nitrile biotransformations
19. Production of acrylamide
20. Production of nicotinamide
21. Other large-scale industrial enzyme processes Penicillin acylase
Penicillin (produced at very high yields by industrial-strain Streptomyces fermentations) is converted enzymatically to 6-aminopenicillanic acid
6-Aminopenicillanic acid is a substrate for chemical or microbial conversion to valuable commercial antibiotics (e.g. Ampicillin)