Ewert Wiebke, Bartens Christian, Ongouta Jekaterina, Holmes Monika, Heutling Anja, Kishore Anusha, Urbansky Tim, Zeilinger Carsten, Preller Matthias, Kirschning Andreas
Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany.
Institute of Organic Chemistry, Leibniz University Hannover, Hannover, Germany.
Nat Commun. 2025 Mar 12;16(1):2464. doi: 10.1038/s41467-025-57013-3.
Amide synthases catalyze the formation of macrolactam rings from aniline-containing polyketide-derived seco-acids as found in the important class of ansamycin antibiotics. One of these amide synthases is the geldanamycin amide synthase GdmF, which we recombinantly expressed, purified and studied in detail both functionally as well as structurally. Here we show that purified GdmF catalyzes the amide formation using synthetically derived substrates. The atomic structures of the ligand-free enzyme and in complex with simplified substrates reveal distinct structural features of the substrate binding site and a putative role of the flexible interdomain region for the catalysis reaction.
酰胺合成酶催化从含苯胺的聚酮衍生的开链酸形成大环内酯环，这在安莎霉素类重要抗生素中可以发现。其中一种酰胺合成酶是格尔德霉素酰胺合成酶GdmF，我们对其进行了重组表达、纯化，并在功能和结构上进行了详细研究。在此我们表明，纯化后的GdmF使用合成衍生的底物催化酰胺形成。无配体酶及其与简化底物复合物的原子结构揭示了底物结合位点的独特结构特征以及柔性结构域间区域在催化反应中的假定作用。
