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The itertools module in Python has a lot of methods to deal with such combinatorial problems.

python3 - <<\eof
import itertools as it

dna = 'atcg'
step = 5

with open('yourfile') as f:
  for nr,_ in enumerate(f):
    l = _.rstrip('\n')

    if not nr:
      w = len(l)
      I = [i for i in range(step-1,w,step)]
      igen = it.cycle(it.product(dna,repeat=int(w/step)))

    t = list(next(igen))[::-1]
    print(*[
      t.pop(0) if idx in I else e
      for idx,e in enumerate(l)],sep="")
eof

• From the iterations module, the method product generates a Cartesian product of the iterations inputted, in our case tne dna sequence multiple times.
• We turn it into an infinite iterator that never ends and recycled from start once the number of Cartesian products is reached whilst the input file still has data in it.