If you want to find the longest substring without any mismatches between two strings you could use this function:

def longest_substring(s1, s2):
    t = [[0]*(1+len(s2)) for i in range(1+len(s1))]
    l, xl = 0, 0
    for x in range(1,1+len(s1)):
        for y in range(1,1+len(s2)):
            if s1[x-1] == s2[y-1]:
                t[x][y] = t[x-1][y-1] + 1
                if t[x][y]>l:
                    l = t[x][y]
                    xl  = x
            else:
                t[x][y] = 0
    return s1[xl-l: xl]

It gives you:

s1 = "sherlock holmes and dr watson"
s2 = "dr watson and jack the ripper"
print longest_substring(s1,s2)
'dr watson'

Generally, perhaps you can apply a Needleman-Wunsch global alignment with a high gap penalty. Bring in the alignments into an AlignIO object, iterate through them and count the longest run of bases between gaps within an alignment. Then sort alignments by this count and pull out the top hit(s).