How about reading ahead, so simplifying the required substitution (i.e. modify the previous line of input), e.g.:

#!/usr/bin/perl

use strict;

my ( $prev, $this ) = ( undef(), undef() );
while( <> ) {
    $this = $_;
    /^>>[^>]/ or mySubst( \$prev );
    print $prev;
    $prev = $this;
}

# finally, process the last line of input which got left over
mySubst( \$prev );
print $prev;

sub mySubst {
    my $sref = shift;
    $$sref =~ s/^>>>/PYTHON_PROMPT/;
}
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Update: Having just seen the previous post: The point of reading ahead is to avoid reading the whole file into an array - also (ahem!) the read-ahead version here is one I took a few minutes to test with suitable input.