Keshav Maharaj and Chris Morris shared six wickets as South Africa made light of Kagiso Rabada's absence to establish a commanding position against England in the second Test at Trent Bridge on Saturday.
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The Proteas were 75 for one in their second innings at stumps on the second day - already an overall lead of 205 runs.
Dean Elgar was 38 not out and Hashim Amla 23 not out.
"It has been an excellent day of cricket for us," Morris said after stumps on day two.
"The guys showed guts and fought hard at the end to get to the close. We are pretty chuffed."
South Africa saw James Anderson, England's all-time leading Test wicket-taker, capture their last four first-innings wickets for four runs in 16 balls as they slumped from an overnight 309 for six to 335 all out.
The Proteas, in turn, skittled out England for 205, with left-arm spinner Maharaj taking three for 21 in 10 overs and recalled all-rounder Morris three for 38 in 8.5 overs.
It was yet another example of the resilience of a South Africa side who have lost just one of their last 19 away Test series.
No team have made more in the fourth innings to win a Test at Trent Bridge than England's 284 for six against New Zealand in 2004.
"We are in a tricky position. It was not a great day for us", said Anderson.
"We did well to bowl them out for 350 but didn't get it right with the bat."
South Africa's performance was all the more impressive as fast bowler Rabada had been banned from this match as a result of swearing at England all-rounder Ben Stokes during the hosts' 211-run win at Lord's last week that put them 1-0 up in this four-match series.
