Discovery of a Mosaic-Like Biosynthetic Assembly Line with a Decarboxylative Off-Loading Mechanism through a Combination of Genome Mining and Imaging

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2016
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Mir Mohseni, Mahsa
Höver, Thomas
Kaiser, Marcel
Dorrestein, Pieter C.
Dickschat, Jeroen S.
Schäberle, Till F.
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Angewandte Chemie International Edition. Wiley-Blackwell. 2016, 55(43), pp. 13611-13614. ISSN 1433-7851. eISSN 1521-3773. Available under: doi: 10.1002/anie.201606655
Zusammenfassung

The biosynthetic gene cluster for the antiplasmodial natural product siphonazole was identified by using a combination of genome mining, imaging, and expression studies in the natural producer Herpetosiphon sp. B060. The siphonazole backbone is assembled from an unusual starter unit from the shikimate pathway that is extended by the action of polyketide synthases and non-ribosomal peptide synthetases with unusual domain structures, including several split modules and a large number of duplicated domains and domains predicted to be inactive. Product release proceeds through decarboxylation and dehydration independent of the thioesterase SphJ and yields the diene terminus of siphonazole. High variation in terms of codon-usage within the gene cluster, together with the dislocated domain organization, suggest a recent emergence in evolutionary terms.

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ISO 690MIR MOHSENI, Mahsa, Thomas HÖVER, Lena BARRA, Marcel KAISER, Pieter C. DORRESTEIN, Jeroen S. DICKSCHAT, Till F. SCHÄBERLE, 2016. Discovery of a Mosaic-Like Biosynthetic Assembly Line with a Decarboxylative Off-Loading Mechanism through a Combination of Genome Mining and Imaging. In: Angewandte Chemie International Edition. Wiley-Blackwell. 2016, 55(43), pp. 13611-13614. ISSN 1433-7851. eISSN 1521-3773. Available under: doi: 10.1002/anie.201606655
BibTex
@article{MirMohseni2016Disco-57619,
  year={2016},
  doi={10.1002/anie.201606655},
  title={Discovery of a Mosaic-Like Biosynthetic Assembly Line with a Decarboxylative Off-Loading Mechanism through a Combination of Genome Mining and Imaging},
  number={43},
  volume={55},
  issn={1433-7851},
  journal={Angewandte Chemie International Edition},
  pages={13611--13614},
  author={Mir Mohseni, Mahsa and Höver, Thomas and Barra, Lena and Kaiser, Marcel and Dorrestein, Pieter C. and Dickschat, Jeroen S. and Schäberle, Till F.}
}
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