In vivo structure–activity relationships and optimization of an unnatural base pair for replication in a semi-synthetic organism

A.W. Feldman, F.E. Romesberg, J Am Chem Soc (2017) 139:11427–11433.
2017bfeldmanWe screened 135 candidate UBPs for optimal performance in an SSO, comparing the resulting in vivo SARs to those collected previously in vitro. In addition to some interesting differences, the present screen identified four UBPs whose retention in the DNA of an SSO is higher than that of dNaM-dTPT3, which was previously the most promising UBP identified.


Synthetic biology parts for the storage of increased genetic information in cells

S.E. Morris, A.W. Feldman, F.E. Romesberg, ACS Synth Biol (2017) Published online June 27.
pubpic2017MorrisWe report a steady-state kinetic characterization of the rate with which the Klenow fragment of E. coli DNA polymerase I synthesizes the dNaM-dTPT3 UBP and its mispairs in a variety of sequence contexts. The data demonstrate that dNaMTP and dTPT3TP are well optimized and standardized parts for the expansion of the genetic alphabet.


A semisynthetic organism engineered for the stable expansion of the genetic alphabet

Y. Zhang, B.M. Lamb, A.W. Feldman, A.X. Zhou, T. Lavergne, L. Li, F.E. Romesberg, Proc. Natl. Acad. Sci. USA (2017) 114: 1317–1322.
pubpic2017zhangWe describe an optimized SSO that is healthy, more autonomous than its predecessor, and able to store increased information indefinitely. The SSO constitutes a stable form of semisynthetic life and lays the foundation for efforts to impart life with new forms and functions. Read more in The Guardian, The Washington Post, TSRI News & Views, and The San Diego Union Tribune, or listen to an interview in This Way Up from Radio New Zealand.


The expanding world of DNA and RNA

T. Chen, N. Hongdilokkul, Z. Liu, D. Thirunavukarasu, F.E. Romesberg, Curr. Op. Chem. Biol. (2016) 34:80–87.
pubpic2016bchenWe review nucleotide modifications, such as those to phosphate and sugar moieties that increase nuclease resistance or the range of activities possible, as well as whole nucleobase replacement that results in selective pairing and the creation of unnatural base pairs. Both in vitro and in vivo examples are discussed, including efforts to create semi-synthetic organisms with altered or expanded genetic alphabets.


A semi-synthetic organism with an expanded genetic alphabet

D.A. Malyshev, K. Dhami, T. Lavergne, T. Chen, N. Dai, J.M. Foster, I.R. Corrêa, F.E. Romesberg, Nature (2014) 509:385-388.
pubpic2014malyshevWe demonstrate that E. coli can stably maintain a plasmid containing d5SICS–dNaM with only the addition of an exogenously expressed algal nucleotide triphosphate transporter. Read the associated News & Views or read more in The New York Times, The Atlantic, Wired, Science, Chemistry World, and The San Diego Union Tribune. This work was also recognized as one of the top 10 scientific achievements of 2014 by Science.