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Applied Microbiology and Biotechnology

, Volume 68, Issue 2, pp 141–150 | Cite as

Mutational biosynthesis—a tool for the generation of structural diversity in the biosynthesis of antibiotics

  • S. Weist
  • R. D. SüssmuthEmail author
Mini-Review

Abstract

Natural products represent an important source of drugs in a number of therapeutic fields, e.g. antiinfectives and cancer therapy. Natural products are considered as biologically validated lead structures, and evolution of compounds with novel or enhanced biological properties is expected from the generation of structural diversity in natural product libraries. However, natural products are often structurally complex, thus precluding reasonable synthetic access for further structure-activity relationship studies. As a consequence, natural product research involves semisynthetic or biotechnological approaches. Among the latter are mutasynthesis (also known as mutational biosynthesis) and precursor-directed biosynthesis, which are based on the cellular uptake and incorporation into complex antibiotics of relatively simple biosynthetic building blocks. This appealing idea, which has been applied almost exclusively to bacteria and fungi as producing organisms, elegantly circumvents labourious total chemical synthesis approaches and exploits the biosynthetic machinery of the microorganism. The recent revitalization of mutasynthesis is based on advancements in both chemical syntheses and molecular biology, which have provided a broader available substrate range combined with the generation of directed biosynthesis mutants. As an important tool in supporting combinatorial biosynthesis, mutasynthesis will further impact the future development of novel secondary metabolite structures.

Keywords

Biosynthetic Gene Cluster Mandelic Acid Peptide Antibiotic Glycopeptide Antibiotic Nikkomycin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by a grant of the European Union (COMBIG-TOP, LSHG-CT-2003-503491), the Deutsche Forschungsgemeinschaft (DFG, SU 239/3-3) and by an Emmy-Noether-Fellowship for young investigators of the DFG (SU 239/2-1).

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Biologische Chemie/Institut für ChemieTechnische Universität BerlinBerlinGermany
  2. 2.Department of ChemistryMassachusetts Institute of TechnologyCambridgeUSA

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