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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
Perspective

Abstract

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.

Keywords

cheminformatics cyclases cyclopeptides macrocycles natural products polyketides terpenoids 

Abbreviations

ACE

angiotensin converting enzyme

ACP

acyl carrier protein

AT

acyl transferase

C

condensation

6-dEB

6-deoxyerythronolide B

DEBS

deoxyerythronolide B synthase

E

epimerization (domain)

GGPP

geranylgeranyl diphosphate

KR

ketoreductase (domain)

KS

ketosynthase (domain)

M

N-methylation (domain)

Nic

nicotinoyl

NRPS

non-ribosomal peptide synthetase

PCP

peptidyl carrier protein

PKS

polyketide synthase

QSAR

quantitative structure-activity relationships

TE

thioesterase

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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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