Engineering a smaller lysozyme is a challenge for both random and site
-directed mutagenesis. This paper illustrates the power of knowledge-b
ased protein engineering in the design of a smaller lysozyme that fold
s correctly and has activity against bacterial cell walls. In this sma
ller lysozyme the conserved disulphide bridged loop is replaced by a s
hort loop. The long loop was selected because it buries a predominantl
y hydrophilic surface. The short loop was discovered by searching for
appropriate fragments in the protein databank. This approach is import
ant in the design of small enzymes useful to the food industry.