Molecular Genetics of Biosynthesis

  • Ralph W. Jack
  • Gabriele Bierbaum
  • Hans-Georg Sahl
Part of the Biotechnology intelligence unit book series (BIOIU)


The lantibiotic nisin had already been established as a food preservative when I the first research into its biosynthesis was initiated by Hurst in 1966.1 At that time, most scientists agreed that polypeptide antibiotics, e.g.,bacitracin (see chapter 1), which contain unusual amino acids, were synthesized by nonribosomal mechanisms, since there are no codons in the genetic code that permit integration of the rare amino acids into the peptide backbone.2 In contrast to this hypothesis, the first studies with inhibitors of RNA and ribosomal protein biosynthesis, as well as experiments employing labeled Ser, Thr and Cys demonstrated that the ring forming lanthionine (Lan) and methyllanthionine (MeLan) residues in nisin derive from the proteinogenic amino acids Ser, Thr and Cys.1,3,4 The first part of this chapter will describe this unusual pathway that leads to the biosynthesis of the modified residues in lantibiotics and microcin B17. The ultimate evidence for the ribosomal biosynthesis mechanism, the sequence of the structural gene of epidermin which contains the codons for Ser, Thr and Cys in those positions that are occupied by Lan and MeLan in the mature lantibiotic,5 was presented nearly two decades after those pioneering experiments of Hurst and Ingram and the structural genes of nisin, subtilin and Peps followed within one year.6–8 The cloning of these structural genes led to a very fruitful period of lantibiotic research in the early 1990s, which includes the discovery of the lantibiotic biosynthetic gene clusters, whose molecular architecture and regulation will be presented in detail below. The biosynthesis of microcin B17 will also be described in this chapter. Here, the structural gene was discovered in 19899 before the structure of the mature peptide had been elucidated.10


Gene Cluster Amino Acid Protein Biosynthetic Gene Cluster Modification Enzyme Lactococcus Lactis 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Ralph W. Jack
    • 1
    • 2
  • Gabriele Bierbaum
    • 3
  • Hans-Georg Sahl
    • 3
  1. 1.Institute for Organic ChemistryUniversity of TübingenTübingenGermany
  2. 2.ECHAZ microcollectionsReutlingenGermany
  3. 3.Institute for Medical Microbiology and ImmunologyUniversity of BonnBonnGermany

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