Fusaric acid induces a notochord malformation in zebrafish via copper chelation.
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.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Emily S
ES
Yin
Malika
M
Rakhmankulova
Kaury
K
Kucera
Jose Guedes
JG
de Sena Filho
Carolina E
CE
Portero
Alexandra
A
Narváez-Trujillo
Scott A
SA
Holley
Scott A
SA
Strobel
D000818:Animals; D002151:Calorimetry; D002614:Chelating Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism*; D005669:Fusaric Acid / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005670:Fusarium / Q000737:chemistry; D015394:Molecular Structure; D009672:Notochord / Q000002:abnormalities* / Q000187:drug effects*; D015027:Zebrafish / Q000002:abnormalities* / Q000378:metabolism*
D002614:Chelating Agents; D003300:Copper; D005669:Fusaric Acid