Recoding the Salmonella typhimurium LT2 Genome

Adam Riesselman, Harvard University

A draft genome for the recoded Salmonella typhimurium LT2 (GenBank AE006468) has been produced. The leucine codons – TTA and TTG – have been replaced with synonymous codons, removing all 33,489 instances from the genome. Prophages, pathogenicity islands, pseudogenes and transposases have also been deleted, shrinking the genome from 4857432 to 4470689 nucleotides. Fitness effects caused by inevitable mutations in proteins have been minimized by both combinatoric optimization and mutation modeling. Two restriction sites, BtsI and BspQI, have also been removed from the genome in all regions except rRNAs to assist in the assembly process. This novel recoded organism will be used as a synthetic biology platform to alter the gut microbiome with targeted theraputics.

Abstract Author(s): Adam Riesselman, Michiel Karrenbelt, Jeff Way, Pam Silver