We previously reported the isolation of Cu-fusaric acid (Cu-FA) complex from the mangrove endophyte Fusarium oxysporum ZZF51. In this study, we explored the mechanism of Cu-FA production in the strain ZZF51 by comparing with that of another endophyte Fusarium sp. B2, which produced FA but not Cu-FA in the same culture condition. The results allowed us to hypothesize that Cu(2+) may act as a "signaling molecule" to awaken the silent FA biosynthetic genes in ZZF51, inducing intracellular production of FA followed by chelation with Cu(2+). This signaling network was triggered specifically by Cu(2+) and may be interfered by other metal ions.