Su Li, Schmalhofer Maximilian, Grammbitter Gina L C, Paczia Nicole, Glatter Timo, Groll Michael, Bode Helge B
Department of Natural Products in Organismic Interactions, Max Planck Institute for Terrestrial Microbiology, 35043 Marburg, Germany.
Center for Protein Assemblies, Department of Bioscience, TUM School of Natural Sciences, Technical University of Munich, 85748 Garching, Germany.
J Am Chem Soc. 2025 Jun 18;147(24):20246-20250. doi: 10.1021/jacs.5c07388. Epub 2025 Jun 5.
strains, Gram-negative bacteria pathogenic to insect larvae, produce two signature compounds: the multifunctional isopropylstilbene (IPS), known for its antibiotic, insecticidal, and immunosuppressive activities, and orange-to-red pigmented anthraquinones (AQs), which attenuate oxidative stress. Here, we demonstrate an inverse correlation between the production of AQs and cinnamic acid (CA), the primary precursor for IPS formation in the model strain TTO1. Metabolic and proteomic analyses following CA treatment show that CA inhibits AntI, a key enzyme in the final step of AQ-256 biosynthesis. The crystal structure of AntI in complex with CA reveals that cinnamic acid functions as a competitive inhibitor by inducing specific structural rearrangements in the lyase, resulting in noncovalent, reversible inhibition. These findings provide atomic insights into the intricate regulatory control of pigment biosynthesis and the production of bioactive compounds.
菌株，对昆虫幼虫致病的革兰氏阴性菌，产生两种标志性化合物：多功能异丙基芪（IPS），以其抗生素、杀虫和免疫抑制活性而闻名，以及橙色至红色的色素蒽醌（AQs），其可减轻氧化应激。在这里，我们证明了在模式菌株TTO1中，蒽醌的产生与肉桂酸（CA）之间存在负相关，肉桂酸是IPS形成的主要前体。CA处理后的代谢和蛋白质组学分析表明，CA抑制AntI，AntI是蒽醌生物合成最后一步中的关键酶。AntI与CA复合物的晶体结构表明，肉桂酸通过诱导裂解酶中的特定结构重排而作为竞争性抑制剂发挥作用，导致非共价、可逆抑制。这些发现为色素生物合成和生物活性化合物生产的复杂调控控制提供了原子层面的见解。
