Molecular Diversity

, Volume 9, Issue 1–3, pp 171–186 | Cite as

What can a chemist learn from nature’s macrocycles? – A brief, conceptual view

  • Ludger A. Wessjohann
  • Eelco Ruijter
  • Daniel Garcia-Rivera
  • Wolfganf Brandt


Macrocyclic natural products often display remarkable biological activities, and many of these compounds (or their derivatives) are used as drugs. The chemical diversity of these compounds is immense and may provide inspiration for innovative drug design. Therefore, a database of naturally occurring macrocycles was analyzed for ring size, molecular weight distribution, and the frequency of some common substructural motifs. The underlying principles of the chemical diversity are reviewed in terms of biosynthetic origin and nature’s strategies for diversity and complexity generation in relation to the structural diversity and similarities found in the macrocycle database. Finally, it is suggested that synthetic chemists should use not only nature’s molecules, but also nature’s strategies as a source of inspiration. To illustrate this, the biosynthesis of macrocycles by non-ribosomal peptide synthetases and terpene and polyketide cyclases, as well as recent advances of these strategies in an integrated synthesis/biotechnology approach are briefly reviewed.


cheminformatics cyclases cyclopeptides macrocycles natural products polyketides terpenoids 



angiotensin converting enzyme


acyl carrier protein


acyl transferase




6-deoxyerythronolide B


deoxyerythronolide B synthase


epimerization (domain)


geranylgeranyl diphosphate


ketoreductase (domain)


ketosynthase (domain)


N-methylation (domain)




non-ribosomal peptide synthetase


peptidyl carrier protein


polyketide synthase


quantitative structure-activity relationships




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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Ludger A. Wessjohann
    • 1
  • Eelco Ruijter
    • 1
  • Daniel Garcia-Rivera
    • 1
  • Wolfganf Brandt
    • 1
  1. 1.Department of Bioorganic Chemistry, Weinberg 3Leibniz-Institute of Plant BiochemistryD-06120 Halle (Saale)Germany

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