TMG-chitotriomycin, an enzyme inhibitor specific for insect and fungal β-N-acetylglucosaminidases, produced by actinomycete Streptomyces anulatus NBRC 13369
TMG-chitotriomycin, an enzyme inhibitor specific for insect and fungal β-N-acetylglucosaminidases, produced by actinomycete Streptomyces anulatus NBRC 13369
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DOI：
10.1021/ja077641f
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发表时间：
2008-03-26
影响因子：
15
通讯作者：
Kanzaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Usuki, Hirokazu;Nitoda, Teruhiko;Kanzaki, Hiroshi
从链霉菌 NBRC13369 的培养滤液中分离出一种新型 β-N-乙酰氨基葡萄糖苷酶 (GlcNAcase) 抑制剂，称为 TMG-壳三霉素 (1)。仅当胶体几丁质用作生产培养基中的唯一碳源时，该菌株才产生1。通过相应糖醇衍生物的光谱和本构糖分析确定1的结构是α-D-N,N,N-triMeGlcNH(2)-(1,4)-beta-D-GlcNAc-(1,4)-beta-D-GlcNAc-(1,4)-D-GlcNAc及其还原端残基C-2差向异构体的平衡混合物。 TMG-壳三霉素 (1) 对昆虫和真菌 GlcNA 酶具有有效和选择性的抑制作用，但对哺乳动物和植物 GlcNA 酶没有抑制作用。相比之下，已知的 GlcNAcase 抑制剂那格他汀可有效抑制所有 GlcNAcase。应该强调的是，合成的D-N,N,N-triMeGlcNH(2)（1的组成糖）对斜纹夜蛾GlcNAcase没有抑制作用。这些结果表明，位于 1 还原端的 (GlcNAc)(3) 单元对其酶抑制活性至关重要。 1 的独特抑制谱将有助于研究几丁质分解系统和开发选择性杀菌剂或杀虫剂。
A novel beta-N-acetylglucosaminidase (GIcNAcase) inhibitor named TMG-chitotriomycin (1) was isolated from the culture filtrate of Streptomyces anulatus NBRC13369. The strain produced 1 only when colloidal chitin was used as the sole carbon source in the production medium. The structure of 1 was determined by spectral and constitutive sugar analyses of the corresponding alditol derivatives to be an equilibrated mixture of alpha-D-N,N,N-triMeGIcNH(2)-(1,4)-beta-D-GIcNAc-(1,4)-beta-D-GIcNAc-(1,4)-D-GlcNAc and its C-2 epimer of the reducing end residue. TMG-chitotriomycin (1) showed potent and selective inhibition of insect and fungal GIcNAcases with no inhibition of mammalian and plant GIcNAcases. In contrast, the known GIcNAcase inhibitor nagstatin potently inhibited all GIcNAcases. It should be emphasized that synthesized D-N,N,N-triMeGIcNH(2), which is the component sugar of 1, showed no inhibition of the insect Spodoptera litura GIcNAcase. These results suggest that the (GIcNAc)(3) unit positioned at the reducing end of 1 is essential for its enzyme inhibitory activity. The unique inhibitory spectrum of 1 will be useful to study chitinolytic systems and to develop selective fungicides or pesticides.