Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan.
Department of Chemistry, University of Yangon, Yangon 11041, Myanmar.
Bioorg Med Chem Lett. 2021 Mar 15;36:127787. doi: 10.1016/j.bmcl.2021.127787. Epub 2021 Jan 15.
SmltD is an ATP-dependent ligase that catalyzes the condensation of UDP-MurNAc-l-Ala and l-Glu to form UDP-MurNAc-l-Ala-l-Glu, in the newly discovered peptidoglycan biosynthesis pathway of a Gram-negative multiple-drug-resistant pathogen, Stenotrophomonas maltophilia. Phytochemical investigation of the 70% ethanol extract from Woodfordia fruticosa flowers collected in Myanmar led to the identification of anti-SmltD active flavonoids, kaempferol 3-O-(6''-galloyl)-β-d-glucopyranoside (1), astragalin (2), and juglalin (3). Among them, 1 showed the most potent SmltD inhibitory activity. An enzyme steady-state kinetic study revealed that 1 exerted competitive inhibition with respect to ATP. The results of this study provided an attractive foundation for the further development of novel inhibitors of SmltD.
SmltD 是一种依赖于 ATP 的连接酶，可催化 UDP-MurNAc-l-Ala 和 l-Glu 缩合形成 UDP-MurNAc-l-Ala-l-Glu，该酶存在于革兰氏阴性多重耐药病原体新发现的肽聚糖生物合成途径中。对在缅甸采集的沃福德亚属弗鲁蒂科萨花的 70%乙醇提取物进行的植物化学研究导致鉴定出抗 SmltD 活性的类黄酮，山柰酚 3-O-(6''-没食子酰基)-β-d-吡喃葡萄糖苷（1）、杨梅素（2）和 Juglalin（3）。其中，1 表现出最强的 SmltD 抑制活性。酶稳态动力学研究表明，1 对 ATP 表现出竞争性抑制。该研究结果为进一步开发 SmltD 的新型抑制剂提供了有吸引力的基础。
