Randomization of β-galactosidase residues 201, 540 and 604. Complementary primer pairs (arrows) encoding vector sequence (black) or lacZ (colored) were synthesized. The lacZ-specific primers were degenerate (NNK) at codons 201, 540 and 604. The 6his-lacZ-pET28a+ (white circle) was employed as a template in four separate PCR reactions (white bar = vector–201, blue bar = 201–540, green bar = 540–604, red bar = 604–vector). Each PCR product overlapped one or two others in sequence; the four PCR products were combined in a single overlap PCR reaction (reaction 5). The full-length recombinant PCR product was purified, self-ligated and electroporated into E. coli.