Zhong Lei, Mühlenweg Agnes, Hong Dou, Yammine Sarah, Poch Annette, Xu Dingchang, Kirimlioglu Yasemin, Großgloß Lisa, Boulanger Malo, Graeger Franziska, Seidel Maria, Gemander Manuel, Walther Grit, Kemper Sebastian, Dang Tam, Royer Monique, Mainz Andi, Cociancich Stéphane, Süssmuth Roderich D
Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, Berlin 10623, Germany.
CIRAD, UMR PHIM, Montpellier 34398, France.
J Am Chem Soc. 2025 Jun 18;147(24):20725-20734. doi: 10.1021/jacs.5c04167. Epub 2025 Jun 2.
The complex (BCC) is a group of Gram-negative bacteria known for their pathogenicity to patients suffering from cystic fibrosis (CF). The BCC-belonging strain BC11 (formerly BC11) produces AFC-BC11, a compound with strong activity against phytopathogenic fungi. In this contribution, we report on the unprecedented -acyl-tetrapeptide structure and antifungal potency of this natural product. We further provide insights into central steps of its biosynthesis mediated by a nonclassical nonribosomal peptide synthesis machinery lacking condensation domains. With the involvement of a sole acyl/peptidyl carrier protein AfcK, an acyltransferase AfcL and coenzyme A, the growing acyl-peptide chain is shuffled between different thioester carriers during the intricate biosynthetic assembly. The knowledge of the AFC-BC11 structure may contribute to the development of antifungals against phytopathogens and, with the gene cluster being conserved in various strains, possibly to an understanding of the human pathogenesis of the BCC.
伯克霍尔德菌复合体（BCC）是一组革兰氏阴性细菌，以对囊性纤维化（CF）患者具有致病性而闻名。属于伯克霍尔德菌复合体的菌株BC11（原名为BC11）产生AFC-BC11，这是一种对植物致病真菌具有强活性的化合物。在本论文中，我们报道了这种天然产物前所未有的α-酰基四肽结构和抗真菌效力。我们还深入研究了由缺乏缩合结构域的非经典非核糖体肽合成机制介导的其生物合成的核心步骤。在唯一的酰基/肽基载体蛋白AfcK、酰基转移酶AfcL和辅酶A的参与下，在复杂的生物合成组装过程中，不断增长的酰基肽链在不同的硫酯载体之间转移。AFC-BC11结构的知识可能有助于开发针对植物病原体的抗真菌药物，并且由于该基因簇在各种菌株中保守，可能有助于理解伯克霍尔德菌复合体对人类的致病机制。
