Synthetic Biology: The Chemist's Approach

Abstract

In 1999, my lab at The Scripps Research Institute set out to expand the genetic alphabet by developing an unnatural base pair (UBP), with the goal of using it as the basis of semi‐synthetic organisms (SSOs) with expanded genetic codes. In 2014, we reported the successful creation of the first SSO that stored a UBP in its DNA, and then in 2017, we reported the first SSO that not only stored UBPs, but also retrieved the information they made available via transcription and translation to produce proteins containing non‐canonical amino acids (ncAAs). When I was asked by Ehud Keinan and Ashraf Brik to provide some personal opinions and reflections for The Israeli Journal of Chemistry's Rosarium Philosophorum on Chemical Biology, I thought it would be interesting to recount two challenges faced during this project that were critical for its success: the first illustrates the chemist's approach to synthetic biology, and the second illustrates how a knowledge of biology can facilitate it.

Hydrogen Bonding in Natural and Unnatural Base Pairs—A Local Vibrational Mode Study

“…Utilizing DNA as a material building block in molecular and structural engineering has already led to the creation of numerous molecular-assembly systems and materials at the nanoscale [ 19 ]. Substantial efforts have been made to expand the genetic alphabet of DNA by introducing other base pair combinations, so-called unnatural base pairs ( UBP ) to increase nucleic acid functionalities [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Recently, modifications of DNA containing four NBP and four additional UBP which efficiently replicated [ 32 , 32 ] were reported.…”