bedtools maskfasta

Just provide the bed file with 0 coverage regions

You can do this with pyfaidx as well.

$ pip install pyfaidx
$ faidx -m -b regions.bed file.fa  # mask with "N"
$ faidx -s X -m -b regions.bed file.fa  # mask with "X"
$ faidx -M -b regions.bed file.fa  # soft-mask with lowercase characters

These all modify file.fa in-place, so make sure you're either testing on a copy or ready to change the file.