中文摘要：单端孢霉烯毒素常在表面正常的谷物籽粒上累积。为了开发一种农业化学制剂降低单端孢霉烯毒素污染，本研究从化学阵列上的化合物中筛选了单端孢霉烯毒素抑制剂。研究表明识别作为TDN合成抑制剂的NPD352，为系统引进广泛的甾烷骨架和氨基酸残基结构多样性，开发更加强效的抑制剂奠定了基础。
外文摘要： Trichothecene mycotoxins often accumulate in apparently normal grains of cereal crops. In an effort to develop an agricultural chemical to reduce trichothecene contamination, we screened trichothecene production inhibitors from the compounds on the chemical arrays. By using the trichodiene (TDN) synthase tagged with hexahistidine (rTRI5) as a target protein, 32 hit compounds were obtained from chemical library of the RIKEN Natural Product Depository (NPDepo) by chemical array screening. At 10 μg mL− 1, none of the 32 chemicals inhibited trichothecene production by Fusarium graminearum in liquid culture. Against the purified rTRI5 enzyme, however, NPD10133 [progesterone 3-(O-carboxymethyl)oxime amide-bonded to phenylalanine] showed weak inhibitory activity at 10 μg mL− 1 (18.7 μM). For the screening of chemicals inhibiting trichothecene accumulation in liquid culture, 20 analogs of NPD10133 selected from the NPDepo chemical library were assayed. At 10 μM, only NPD352 [testosterone 3-(O-carboxymethyl)oxime amide-bonded to phenylalanine methyl ester] inhibited rTRI5 activity and trichothecene production. Kinetic analysis suggested that the enzyme inhibition was of a mixed-type. The identification of NPD352 as a TDN synthase inhibitor lays the foundation for the development of a more potent inhibitor via systematic introduction of wide structural diversity on the gonane skeleton and amino acid residues.
外文关键词：Chemical array；Fusarium graminearum；Gonane skeleton；Mixed-type inhibition；Trichodiene synthase；Trichothecene production inhibitor
作者：Maeda, K；Nakajima, Y；Motoyama, T；Kondoh, Y；Kawamura, T；Kanamaru, K；Ohsato, S；Nishiuchi, T；Yoshida, M；Osada, H; Kobayashi, T；Kimura, M
作者单位：Nagoya Univ
期刊名称：PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
期刊影响因子：2.388
出版年份：2017
出版刊次：5
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