Letter | Published:

Formation of proinsulin by immobilized Bacillus subtilis

Naturevolume 302pages543545 (1983) | Download Citation



There has been an increasing interest in the use of immobilized cells for the production of pharmaceuticals as well as for products such as high fructose syrup or ethanol1. Some of these compounds are now produced on an industrial scale2 whereby the cells are used in a resting or growing state or in a nonviable form as natural carriers of the enzyme(s) involved in the synthesis. The advantages of immobilized cell technology should also apply to microorganisms modified by recombinant DNA techniques to produce a variety of eukaryotic proteins such as hormones. We describe here the properties of immobilized Bacillus subtilis cells carrying plasmids encoding rat proinsulin. Cell proliferation normally coupled to DNA replication is undesirable in immobilized cell systems as ‘clogging’ of the system occurs due to cells growing outside the beads. Therefore, different ways were investigated to inhibit cell division while allowing continued protein synthesis. We found that the addition of certain antibiotics in the growth medium, such as novobiocin which inhibits DNA replication3, fulfills these requirements, allowing proinsulin synthesis and excretion to take place over a period of several days.

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  1. Pure and Applied Biochemistry, Chemical Center, University of Lund, PO Box 740, S-220 07, Lund, Sweden

    • Klaus Mosbach
    • , Staffan Birnbaum
    •  & Leif Bülow
  2. Biogen S.A., PO Box CH-1211, Geneva, 24, Switzerland

    • Kim Hardy
    •  & Julian Davies


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