Toss aside a Senate seat (reelection in 2010) for a maximum 4 year stint as a third tier cabinet secretary? One chosen specifically to a) show some bipartisanship; b) not do any damage to the Obama agenda, and most importantly, c) give the Democrats the filibuster proof 60 Senate votes?
I don't think that Sen. Gregg will be able to actually get an enforceable agreement to have a Republican fill this seat. And if he does, it will probably be someone serving as a functioning Democrat. One notes that Obama certainly didn't pick a Senator from a state with a Republican governor.
Essentially, he'd be trading his Senate seat for a position as a bureaucratic flunky. While the real decisions about commerce are made elsewhere.
I don't especially have a problem with Republicans serving in the Obama Administration; the key is whether or not they are in a position to advance America's interests on a net balance basis. I don't think that a Senate seat in today's environment for a minor cabinet post represents a tradeoff that's in the country's interests.