Designing better phages.
We propose a method to engineer the genome of bacteriophages to increase their effectiveness as antibacterial agents. Specifically, we exploit the redundancy of the triplet code to design genomes that avoid restriction sites while producing the same proteins as wild-type phages. We give an efficient algorithm to minimize the number of restriction sites against sets of cutter sequences, and demonstrate that that phage genomes can be significantly protected against surprisingly large sets of enzymes with no loss of function. Finally, we develop a model to explain why evolution has failed to eliminate many possible restriction sites despite selective pressure, thus motivating the need for genome-level sequence engineering.
Skiena
S S
SS
Applied Algorithm Laboratory, Dept. of Computer Science, State University of New York, Stony Brook, NY 11794-4400, USA. skiena@cs.sunysb.edu
D000465:Algorithms; D001435:Bacteriophages / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology; D004262:DNA Restriction Enzymes; D019143:Evolution, Molecular; D005815:Genetic Code; D005818:Genetic Engineering; D016679:Genome, Viral; D008957:Models, Genetic
D004262:DNA Restriction Enzymes