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A Novel Antibiotic Mechanism of l-Cyclopropylalanine Blocking the Biosynthetic Pathway of Essential Amino Acid l-Leucine
Molecules ( IF 4.2 ) Pub Date : 2017-12-14 , DOI: 10.3390/molecules22122224
Bingji Ma , Jinwen Shen , Wandee Yindeeyoungyeon , Yuan Ruan

The unusual amino acid l-cyclopropylalanine was isolated from the mushroom Amanita virgineoides after detection in an anti-fungal screening test. l-Cyclopropylalanine was found to exhibit broad-spectrum inhibition against fungi and bacteria. The anti-fungal activity was found to be abolished in the presence of the amino acid l-leucine, but not any other amino acids, indicating that l-cyclopropylalanine may block the biosynthesis of the essential amino acid l-leucine, thereby inhibiting fungal and bacteria growth. Further biochemical studies found l-cyclopropylalanine indeed inhibits α-isopropylmalate synthase (α-IMPS), the enzyme that catalyzes the rate-limiting step in the biosynthetic pathway of l-leucine. Inhibition of essential l-leucine synthesis in fungal and bacteria organisms, a pathway absent in host organisms such as humans, may represent a novel antibiotic mechanism to counter the ever-increasing problem of drug resistance to existing antibiotics.

中文翻译:

l-环丙基丙氨酸阻断必需氨基酸 l-亮氨酸生物合成途径的新型抗生素机制

在抗真菌筛选试验中检测到后,从蘑菇鹅膏菌中分离出不寻常的氨基酸 l-环丙基丙氨酸。发现 l-环丙基丙氨酸对真菌和细菌具有广谱抑制作用。发现在氨基酸 l-亮氨酸存在的情况下,抗真菌活性被消除,但没有任何其他氨基酸,表明 l-环丙基丙氨酸可能会阻断必需氨基酸 l-亮氨酸的生物合成,从而抑制真菌和细菌生长。进一步的生化研究发现 l-环丙基丙氨酸确实抑制 α-异丙基苹果酸合酶 (α-IMPS),该酶催化 l-亮氨酸生物合成途径中的限速步骤。抑制真菌和细菌生物体中必需的 l-亮氨酸合成,这是人类等宿主生物体中不存在的途径,
更新日期:2017-12-14
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