Germany's Kaymer, who will make his Ryder Cup debut at The Celtic Manor Resort next month, picked up two shots over his first nine holes to improve to eight under par overall after opening with two rounds of 67.
Zanotti, who has carded two 68s so far, was four under through 14 thanks to a run of three consecutive birdies from the 12th.
Their progress was in stark contrast to Belgian Nicolas Colsaerts and Indian Shiv Kapur, who had led at the halfway stage.
Colsaerts had opened the event with a career-low 62, but after adding a level par 70 on Friday he dropped shots at the first and fourth holes before consolidating with four pars.
A double-bogey six on the fourth ensured Kapur, seeking his first victory on The European Tour, also slipped from the top of the leaderboard but he remained in third only a shot off the pace. He was one over for the day through eight.
American Todd Hamilton, the 2004 Open Championship winner who is now 545th in the world and with only two cuts made in his last 19 events, was also one over through eight and in a tie for fourth on six under.
Reigning Open Champion Louis Oosthuizen continued his improvement, handing in a 66 on the back of an opening 73 and a second round 67.