Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 56, Issue 15, Pages 4351-4355Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201611063
Keywords
biocatalysis; enzyme catalysis; ikarugamycin; natural products
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Funding
- Friedrich Naumann Foundation for Freedom
- Fonds of the Chemical Industry (FCI)
- DFG [GU 1233/2-1]
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Nature provides an inexhaustible diversity of small organic molecules with beautiful molecular architectures that have strong and selective inhibitory activities. However, this tremendous biomedical potential often remains inaccessible, as the structural complexity of natural products can render their synthetic preparation extremely challenging. This problem is addressable by harnessing the biocatalytic procedures evolved by nature. In this work, we present an enzymatic total synthesis of ikarugamycin. The use of an iterative PKS/NRPS machinery and two reductases has allowed the construction of 15 carbon-carbon and 2 carbon-nitrogen bonds in a biocatalytic one-pot reaction. By scaling-up this method we demonstrate the applicability of biocatalytic approaches for the ex vivo synthesis of complex natural products.
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