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Industrial Biotransformations

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Carboxypeptidase B<br />

Pig Pancreas<br />

3) Flow scheme<br />

Not published.<br />

4) Process parameters<br />

conversion: >99.9 %<br />

yield: > 90 %<br />

selectivity: > 90 %<br />

reactor type: batch<br />

reactor volume: 7,500 L<br />

capacity: > 0.5 t · a –1<br />

residence time: 4–6 h<br />

space-time-yield: 1.7 g · L –1 ·d –1<br />

down stream processing: chromatography<br />

enzyme activity: 20 U · g –1 enzyme supplier:<br />

enzyme<br />

Calbiochem, USA<br />

start-up date: 1998<br />

production site: Sanofi Aventis, Germany<br />

company: Sanofi Aventis, France<br />

5) Product application<br />

● In 1921 insulin could be isolated from dog pancreas.<br />

● The sequence was identified by Sanger in 1955.<br />

● Insulin regulates the blood sugar level. It is used for the treatment of diabetes mellitus. Up to<br />

5 % of the population of the western world suffers from diabetes.<br />

● A glucose level below 0.25 mM leads to problems in energy supply to the brain. Consequences<br />

can include coma, irreversible brain damage and death.<br />

● Since insulin is decomposed by proteases it cannot be administered orally. A new application<br />

method is inhalation of modified insulin with faster effects due to exchange of single hydrophobic<br />

amino acid with several hydrophilic amino acids. The continuous application after<br />

measurement of the blood sugar level is the most comfortable and efficient way.<br />

6) Literature<br />

EC 3.4.17.2<br />

● Frank, B.H., Chance, R.E. (1983) Two routes for producing human insulin utilizing recombinant<br />

DNA technology, Münch. Med. Wschr. 125, 14–20<br />

● Jørgensen, L.N., Rasmussen, E., Thomsen, B. (1989) HM(ge), Novo’s biosynthetic insulin;<br />

Med. View. III, No. 4, 1–7<br />

● Ladisch, M.R., Kohlmann, K.L. (1992) Recombinant human insulin, Biotechnol. Prog. 8, 469–<br />

478<br />

349

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