I am definitely a subscriber to not doing premature optimization, but in Python, there is a huge difference between

  found = searched_key in list(large_dict)

vs

  found = searched_key in large_dict

But also compare:

  searched_key in large_dict.keys()  # O(1)

and

  searched_value in large_dict.values()  # O(n)

So much this. Write code that you can reasonably expect to not be slow af, while not sacrificing readability. Then profile and optimize if necessary.