Dropping Paul Manafort as a cooperating witness ruins his credibility as far as anything he told Mueller and any testimony he may be forced to give with respect to that. The lies Mueller is alleging are almost certainly an exercise of Mueller’s specialty, the “perjury trap” he is trying to set for President Trump. It must be assumed the Special Counsel has proof of Manafort’s lies.
Manafort’s defense team has been working with the president’s lawyers since the inception of his plea agreement. The president’s attorney, Rudolph Giuliani, has admitted as much. Mueller is trying to prove collusion between Trump and Manafort with respect to the written answers the president submitted last week in response to Mueller’s questions. If any of Trump’s answers to Mueller’s questions include even one of the same lies as Manafort, it would not only be perjury but the "high crime" the incoming Democratic House majority will use to initiate Articles of Impeachment.
It doesn’t even have to be a big lie -- saying he didn’t know of the Trump Tower meeting between Trump Jr. and Natalia Veselnitskya (who coincidentally, had ties to Fusion GPS, having dined with Glenn Simpson both before and after the meeting), when Mueller has evidence he did, would be enough for Mueller to ruin Trump’s presidency.