If Python has anything like Perl's source code filters, then anything's up for grabs, but Perl is kind of weird in a way that Python was specifically designed not to be. Or at least Python 1 was. Things may have changed in the intervening couple of decades.

If it's just plain overloading, then whitespace is probably off the table. Spaces, even required spaces, aren't so much syntax as they are structure. You could argue that the curly braces of some other languages are more syntactic than Python's whitespace, because it's actually Python's magic colon and the first unindented line (lack of whitespace!) that serve that specific syntactic purpose.

Examples of Perl's source code filters range from turning a program into binary representation of the syntax tree and still having it be executable, to new syntax, to writing programs entirely in Latin or something that looks almost but not entirely unlike it, anyway.