Flavonoids from Woodfordia fruticosa as potential SmltD inhibitors in the alternative biosynthetic pathway of peptidoglycan
Flavonoids from Woodfordia fruticosa as potential SmltD inhibitors in the alternative biosynthetic pathway of peptidoglycan
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DOI：
10.1016/j.bmcl.2021.127787
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发表时间：
2021-01-24
影响因子：
2.7
通讯作者：
Morita, Hiroyuki
中科院分区：
文献类型：
--
作者：
Lee, Yuan-E;Kodama, Takeshi;Morita, Hiroyuki
SmltD是一种ATP依赖性连接酶，在革兰氏阴性多重耐药病原体嗜麦芽寡养单胞菌的新发现的肽聚糖生物合成途径中催化UDP-MurNAc-L-Ala和L-Glu缩合形成UDP-MurNAc-L-Ala-L-Glu。从缅甸采集的Woodfordia fruticosa花的70%乙醇提取物的植物化学研究鉴定出抗SmltD活性黄酮类化合物，山奈酚3-O-（6“-没食子酰基）-β-D-吡喃葡萄糖苷（1），野芝麻苷（2）和胡桃苷（3）。其中，1显示出最强的SmltD抑制活性。酶稳态动力学研究表明，1对ATP具有竞争性抑制作用。本研究结果为进一步开发新型SmltD抑制剂提供了有吸引力的基础。
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)-beta-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.