General information relating to the cost of enzymes Jesper Brask, Claus C. Fuglsang, Ole Kirk Novozymes A/S General enzyme price ranges and price development The cost of industrial enzymes is very dependent on marked size and hence production volume, ranging from $200-$2,000 per kg enzyme protein (EP) for a bulk commodity enzyme (> 1000 ton per year) to $10,000-$100,000 or more per kg EP for a specialized enzyme for a smaller market segment (< 100 ton per year). Enzymes for biocatalysis (i.e. organic synthesis) are typical examples from the latter category, with a number of different enzyme classes, including immobilized forms, being used on a small scale. Many of these can be obtained for research purposes in mg to g quantities. Lipases, the enzyme class most commonly used for organic synthesis, are sold by Sigma at prices up to $500,000 per kg EP. For enzymes immobilized on polymer-based supports, the enzyme loading would be 2-10%, typically 5% (w/w). For supports relevant to industrial production the cost would be in the range of $50-$120 per kg. Hence, with the enzyme prices given above, the total cost for an immobilized enzyme can to calculated to $500-$5000 per kg total weight (with 5% loading). Again, small quantities for research are more costly; Novozyme 435TM, CaLB lipase immobilized on acrylic resin, is sold by Sigma for approx. $12,000 per kg. The industrial enzymes that have been on the marked for the longest time are proteases for the detergent industry. Hence, the price development of detergent proteases effectively illustrates what can be expected for a bulk-volume industrial enzyme. In 1966, the protease cost was approximately $2600 per kg EP. In 2001, the price was in the range of $230 per kg EP. This price reduction was achieved through improved fermentation technology, including higher expression yields. Furthermore, in the same time the efficiency of the enzymes was also improved, so the price per wash load dropped from $0.08 in 1966 to $0.002 in 2001, giving a 40-fold increase in price performance over the 35 years. Example: Production of ethanol from cellulose Recently the U.S. Department of Agriculture (USDA), the Department of Energy (DOE), and the National Renewable Energy Laboratory (NREL) initiated a joint project to analyze and compare the mature starch-to-ethanol industry and the emerging cellulose-to-ethanol industries. It was realized that for the cellulose conversion to be competitive, enzyme costs had to be reduced, and a grant was given to Novozymes Biotech to develop more effective cellulase enzymes for the process. The present enzyme cost for the cellulose-to-ethanol process is approximately $5 per gallon ethanol. However, target of the DOE project is an ethanol selling price of $1.07 per gallon in 2010, requiring an increase of enzyme efficiency by a factor of 10. As a comparison, in the production of ethanol from dry milled corn (starch), the enzyme cost is estimated to $0.05 per gallon of produced ethanol, i.e. 100 times less than the present enzyme cost for the cellulose process. On a starch basis, this is $3 per ton of starch converted to glucose.