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A Semi-Synthetic Organism that Stores and Retrieves Increased Genetic Information

Title A Semi-Synthetic Organism that Stores and Retrieves Increased Genetic Information
Authors Yorke Zhang, Jerod L. Ptacin, Emil C. Fischer, Hans R. Aerni, Carolina E. Caffaro, Kristine San Jose, Aaron W. Feldman, Court R. Turner, Floyd E. Romesberg
Magazine Nature
Date 05/29/2018
DOI 10.1038/nature24659
Introduction Life on Earth has historically stored genetic information using a four-letter alphabet, propagated through two fundamental base pairs. Synthetic biology aims to engineer novel life forms and capabilities. A key approach involves developing semi-synthetic organisms (SSOs) whose DNA integrates two additional letters, forming a unique, unnatural base pair (UBP). Earlier work established an *Escherichia coli* strain capable of importing necessary unnatural triphosphates via a *Phaeodactylum tricornutum* nucleoside triphosphate transporter (PtNTT2) to replicate a plasmid containing the UBP dNaM-dTPT3. While this SSO successfully stores expanded genetic information, its retrieval necessitates the in vivo transcription of the UBP into mRNA and tRNA, subsequent aminoacylation of the tRNA with a non-canonical amino acid (ncAA), and the UBP's effective participation in ribosomal decoding. This study details the in vivo transcription of DNA containing dNaM and dTPT3 into mRNAs with distinct unnatural codons and tRNAs featuring matching unnatural anticodons. We report their efficient decoding at the ribosome, enabling the precise incorporation of natural or non-canonical amino acids into superfolder green fluorescent protein (sfGFP). These findings illustrate that interactions beyond hydrogen bonding significantly contribute to every stage of genetic information management. The resultant SSO can both encode and access augmented information, establishing a versatile platform for developing innovative biological systems and functions.
Quote Yorke Zhang, Jerod L. Ptacin, Emil C. Fischer, Hans R. Aerni, Carolina E. Caffaro, Kristine San Jose, Aaron W. Feldman, Court R. Turner, Floyd E. Romesberg. (2018). A Semi-Synthetic Organism that Stores and Retrieves Increased Genetic Information. Nature,
Element Carbon (C) , Hydrogen (H) , Nitrogen (N) , Oxygen (O) , Phosphorus (P)
Industry Research & Laboratory , Pharmaceutical Industry
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