(CNN) Hillary Clinton has an opportunity that has eluded Democratic presidential nominees for decades: Being the candidate of big business.

In an election already rocked by bizarre twists and turns, Donald Trump's speech meant to galvanize working-class voters in the Rust Belt last week exposed a yawning divide between the billionaire and the business community -- a powerful force in U.S. presidential elections that has historically aligned itself with the Republican Party.

As Trump railed against the Trans-Pacific Partnership trade deal and threatened to withdraw the U.S. from the North American Free Trade Agreement at a campaign rally in Pennsylvania, the U.S. Chamber of Commerce and other leading business lobbies publicly condemned the GOP presumptive nominee. Their warning: Trump's policies would spell economic disaster.

The extraordinary rebuke from the business community was a reminder of just how upside down politics are this year. It comes as Trump is looking to garner support from the GOP establishment just weeks out from his party's convention in Cleveland this month. It also opened the door for Clinton to court corporate leaders and donors who, in a typical election year, may have been inclined to back the GOP nominee.

Even before Trump's speech in Pennsylvania last week, the Clinton campaign was actively reaching out to industry leaders across the political spectrum. Former Walmart executive Leslie Dach has been involved in outreach efforts to business leaders on the campaign's behalf, according to a source familiar with Dach's role.

Clinton aides acknowledge the split between Trump and the business community presents an opportunity to gain allies, winning over Republican-leaning interests or at least persuading them to stay neutral. Clinton, who campaigns Tuesday for the first time with President Barack Obama, used Trump's response to the "Brexit" vote last month -- he cheered Britain's decision to leave the European Union, which sent markets into turmoil -- to argue that Trump is too volatile to play a leading role in the global economy.

Former Oklahoma Gov. Frank Keating, who until last year was head of the American Bankers Association, said the Chamber's public scorn at Trump's economic vision marked a "very significant" break in the alliance between big business and the GOP.

"It's certainly counter cultural," said Keating, a Republican who has not endorsed Trump. The Trump campaign should be particularly wary, Keating added, of the national Chamber's scorn trickling down to local business groups and leaders.

"The Oklahoma City chamber or the Natchez, Mississippi, or the Albany, New York, chamber, a chamber of commerce in a small town California: If they think what the Republican presidential candidate makes no sense for small business development, I would be very concerned," Keating said.

Late last month, the Clinton campaign rolled out endorsements from a bipartisan group of business executives. Several of them made this striking admission: they have never before supported a Democrat for president.

"Since my time at the Naval Academy and service in the Navy, I have consistently voted for Republicans for president," Dan Akerson, former chairman of General Motors, said in a statement shared by the campaign. "Serving as the leader of the free world requires effective leadership, sound judgment, a steady hand and most importantly, the temperament to deal with crises large and small. Donald Trump lacks each of these characteristics."

Jim Doyle, founder of the trade group Business Forward, described the depth of public support Clinton is receiving from the business leaders this election as "extraordinary."

"CEOs of major corporations are growing less likely to endorse at all," said Doyle, a former official in the Bill Clinton administration who is married to Patti Solis Doyle, Hillary Clinton's 2008 campaign manager and a CNN contributor. "So the fact that you've got Republican CEOs endorsing Hillary is remarkable."

But for Clinton, courting big business is also a political risk.

Clinton only recently wrapped up a contentious Democratic primary race against Vermont Sen. Bernie Sanders, a populist liberal who accused her of being too close to big business. During the primary, Clinton ran to the left on a number of policy areas, including TPP. A deal that she had once hailed as the "gold standard" of trade agreements, Clinton declared last year that she could not support it in its current form.

Some in the party have urged Clinton to pick a staunchly liberal running mate, like Massachusetts Sen. Elizabeth Warren, to please the Democratic base -- a move that could alienate the very business leaders who are already rejecting Trump.

Any perception that she is pivoting away from the progressive positions she staked out during the primary season could agitate liberal voters, including former Sanders supporters.

Former U.S. Trade Representative Ron Kirk said he was disappointed when Clinton came out against TPP. He chucked: "But I understand the dynamics of a Democratic primary."

Kirk, who is now co-chair of the international trade practice at the law firm Gibson Dunn, described Trump's economic vision as "diplomatic and economic disengagement with the rest of the world."

Even after a primary race that pushed her to the left, Kirk said, Clinton is much better positioned than Trump to appeal to centrist business leader in the general election.

Republican business leaders "for a while comforted themselves with the belief that — 'Oh, Trump is just saying this stuff to get the nomination. He doesn't mean it,'" Kirk said. "They are horrified at the damage that he is already doing and the amount of time they're already having to spend to comfort allies and customers and partners around the world."