4.4 Article

Unusual Activities of the Thioesterase Domain for the Biosynthesis of the Polycyclic Tetramate Macrolactam HSAF in Lysobacter enzymogenes C3

Journal

BIOCHEMISTRY
Volume 51, Issue 1, Pages 4-6

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/bi2015025

Keywords

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Funding

  1. National Science Foundation of China [31028019]
  2. National Institutes of Health [AI073510]
  3. Nebraska Research Council

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HSAF is an antifungal natural product with a new mode of action. A rare bacterial iterative PKS-NRPS assembles the HSAF skeleton. The biochemical characterization of the NRPS revealed that the thioesterase (TE) domain possesses the activities of both a protease and a peptide ligase. Active site mutagenesis, circular dichroism spectra, and homology modeling of the TE structure suggested that the TE may possess uncommon features that may lead to the unusual activities. The iterative PKS-NRPS is found in all polycyclic tetramate macrolactam gene clusters, and the unusual activities of the TE may be common to this type of hybrid PKS-NRPS.

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