US presidential hopeful Hillary Clinton has come out against the Trans-Pacific Partnership agreement championed by Barack Obama.
The landmark trade deal involves 12 countries along the Pacific rim, including the US, Australia and Japan.
In an interview Mrs Clinton said the agreement left many "unanswered questions" and did not meet the "high bar" she had set.
"I am not in favour of what I have learned about it," she told PBS.
The former Secretary of State joins rivals for the Democratic presidential nomination, Bernie Sanders and Martin O'Malley, in opposing the agreement.
The deal took five years to negotiate and covers 40% of the global economy.
Analysis: Anthony Zurcher, North America reporter
Hillary Clinton's move to come out against the TPP - with some qualifications - less than a week out from the first Democratic debate will instantly be viewed in the context of Democratic presidential politics.
Vermont Senator Bernie Sanders - who has repeatedly condemned the trade agreement as harming US workers and threatening the environment - is offering a surprisingly strong challenge to Mrs Clinton from the populist left.
He was likely to bring the topic up during the debate and use it against the former Secretary of State, who once called the agreement the "gold standard" for trade negotiations.
By backing away from the TPP, Mrs Clinton could also be anticipating the arrival of another, more formidable opponent for the Democratic nomination: Joe Biden.
The vice-president has made increasingly clear moves toward a presidential bid, and given his current job it would be extremely difficult for him to oppose a key piece of his boss's presidential legacy.
Mr Biden's campaign would be likely to rely heavily on working-class, union support - a segment of the Democratic electorate that is firmly opposed to new trade deals. Mrs Clinton could be digging her trenches now, before the battle commences.
In an interview on Wednesday, Mrs Clinton said she would only support a trade bill that helped American workers.
"I have said from the very beginning that we had to have a trade agreement that would create good American jobs, raise wages and advance our national security and I still believe that is the high bar we have to meet," she said.
President Obama, for whom the deal would be a prime economic achievement of his second term, said the deal would level the global playing field for US workers.
"[The deal] includes the strongest commitments on labour and the environment of any trade agreement in history," he said after the agreement was reached.
Meanwhile, Mrs Clinton also plans to propose a tax on high-frequency trading, her campaign said.
The tax would target securities transactions with excessive levels of order cancellations that can destabilise the markets, a campaign aide said.