한빛사 논문
Joongoo Lee1,8, Kenneth E. Schwieter2,8, Andrew M. Watkins3, Do Soon Kim1, Hao Yu4, Kevin J. Schwarz2, Jongdoo Lim5, Jaime Coronado5, Michelle Byrom6, Eric V. Anslyn5, Andrew D. Ellington6, Jeffrey S. Moore2,7,* & Michael C. Jewett1,*
1 Department of Chemical and Biological Engineering, Northwestern University, Evanston 60208 IL, USA.
2 Department of Chemistry, University of Illinois at Urbana−Champaign, Urbana 61801 IL, USA.
3 Departments of Biochemistry and Physics, Stanford University, Stanford 94305 CA, USA.
4 Departments of Chemical and Biomolecular Engineering, University of Illinois at Urbana−Champaign, Urbana 61801 IL, USA.
5 Department of Chemistry, University of Texas at Austin, Austin 78712 TX, USA.
6 Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin 78712 TX, USA.
7 The Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
8 These authors contributed equally: Joongoo Lee, Kenneth E. Schwieter
*Correspondence to Jeffrey S. Moore or Michael C. Jewett
Abstract
The site-specific incorporation of noncanonical monomers into polypeptides through genetic code reprogramming permits synthesis of bio-based products that extend beyond natural limits. To better enable such efforts, flexizymes (transfer RNA (tRNA) synthetase-like ribozymes that recognize synthetic leaving groups) have been used to expand the scope of chemical substrates for ribosome-directed polymerization. The development of design rules for flexizyme-catalyzed acylation should allow scalable and rational expansion of genetic code reprogramming. Here we report the systematic synthesis of 37 substrates based on 4 chemically diverse scaffolds (phenylalanine, benzoic acid, heteroaromatic, and aliphatic monomers) with different electronic and steric factors. Of these substrates, 32 were acylated onto tRNA and incorporated into peptides by in vitro translation. Based on the design rules derived from this expanded alphabet, we successfully predicted the acylation of 6 additional monomers that could uniquely be incorporated into peptides and direct N-terminal incorporation of an aldehyde group for orthogonal bioconjugation reactions.
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