Efficient replication bypass of size-expanded DNA base pairs in bacterial cells

One of the long-standing aims of biomimetic chemistry has been to develop molecules that function as much as possible as the natural ones do.[1] Among the biopolymers, the nucleic acids have long served as a test bed for bio-inspired design. The earliest focus of altered structures for DNA was in the redesign of the phosphodiester backbone,[2] and numerous studies found backbone variants that assembled well into helices. In addition, in recent years, some altered sugars have also been shown to be substrates for certain polymerase enzymes.[3] Such work suggests the possibility of future biological activities associated with altered DNA backbones. More recently, a number of laboratories have focused on design of replacements for the DNA bases themselves, which encode the chemical information of the cell.[4] This is a challenging goal because biological enzymes have evolved the ability to manipulate these bases and base pairs with extraordinarily high selectivity. The polymerase replication of designed DNA pairs has been studied in a number of laboratories. Significant successe