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镰刀菌酸通过铜螯合作用诱导斑马鱼脊索畸形。

Fusaric acid induces a notochord malformation in zebrafish via copper chelation.

作者信息

Yin Emily S, Rakhmankulova Malika, Kucera Kaury, de Sena Filho Jose Guedes, Portero Carolina E, Narváez-Trujillo Alexandra, Holley Scott A, Strobel Scott A

机构信息

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.

出版信息

Biometals. 2015 Aug;28(4):783-9. doi: 10.1007/s10534-015-9855-7. Epub 2015 Apr 26.

DOI:10.1007/s10534-015-9855-7
PMID:25913293
Abstract

Over a thousand extracts were tested for phenotypic effects in developing zebrafish embryos to identify bioactive molecules produced by endophytic fungi. One extract isolated from Fusarium sp., a widely distributed fungal genus found in soil and often associated with plants, induced an undulated notochord in developing zebrafish embryos. The active compound was isolated and identified as fusaric acid. Previous literature has shown this phenotype to be associated with copper chelation from the active site of lysyl oxidase, but the ability of fusaric acid to bind copper ions has not been well described. Isothermal titration calorimetry revealed that fusaric acid is a modest copper chelator with a binding constant of 4.4 × 10(5) M(-1). These results shed light on the toxicity of fusaric acid and the potential teratogenic effects of consuming plants infected with Fusarium sp.

摘要

为了鉴定内生真菌产生的生物活性分子,研究人员对一千多种提取物在发育中的斑马鱼胚胎中进行了表型效应测试。从镰刀菌属分离出的一种提取物可诱导发育中的斑马鱼胚胎出现脊索波动,镰刀菌属是一种广泛分布于土壤中且常与植物相关的真菌属。活性化合物被分离并鉴定为镰刀菌酸。先前的文献表明,这种表型与从赖氨酰氧化酶活性位点螯合铜有关,但镰刀菌酸结合铜离子的能力尚未得到充分描述。等温滴定量热法表明,镰刀菌酸是一种适度的铜螯合剂,结合常数为4.4×10⁵ M⁻¹。这些结果揭示了镰刀菌酸的毒性以及食用感染镰刀菌属的植物可能产生的致畸作用。

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