Translation of Diverse Aramid- and 1,3-Dicarbonyl-peptides by Wild Type Ribosomes

Overview

Journal ACS Cent Sci

Specialty Chemistry

Date 2019 Aug 13

PMID 31403077

Citations 30

Authors

Omer Ad

Kyle S Hoffman

Andrew G Cairns

Aaron L Featherston

Scott J Miller

Dieter Soll

Alanna Schepartz

Affiliations

Soon will be listed here.

Abstract

Here, we report that wild type ribosomes accept and elongate precharged initiator tRNAs acylated with multiple benzoic acids, including aramid precursors, as well as malonyl (1,3-dicarbonyl) substrates to generate a diverse set of aramid-peptide and polyketide-peptide hybrid molecules. This work expands the scope of ribozyme- and ribosome-catalyzed chemical transformations, provides a starting point for translation engineering efforts, and offers an alternative strategy for the biosynthesis of polyketide-peptide natural products.

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References

Du L, Sanchez C, Shen B . Hybrid peptide-polyketide natural products: biosynthesis and prospects toward engineering novel molecules. Metab Eng. 2001; 3(1):78-95. DOI: 10.1006/mben.2000.0171. View

Silakowski B, Nordsiek G, Kunze B, Blocker H, Muller R . Novel features in a combined polyketide synthase/non-ribosomal peptide synthetase: the myxalamid biosynthetic gene cluster of the myxobacterium Stigmatella aurantiaca Sga15. Chem Biol. 2001; 8(1):59-69. DOI: 10.1016/s1074-5521(00)00056-9. View

Staunton J, Weissman K . Polyketide biosynthesis: a millennium review. Nat Prod Rep. 2001; 18(4):380-416. DOI: 10.1039/a909079g. View

Meyer E, Castellano R, Diederich F . Interactions with aromatic rings in chemical and biological recognition. Angew Chem Int Ed Engl. 2003; 42(11):1210-50. DOI: 10.1002/anie.200390319. View

Dedkova L, Fahmi N, Golovine S, Hecht S . Enhanced D-amino acid incorporation into protein by modified ribosomes. J Am Chem Soc. 2003; 125(22):6616-7. DOI: 10.1021/ja035141q. View

Murakami H, Saito H, Suga H . A versatile tRNA aminoacylation catalyst based on RNA. Chem Biol. 2003; 10(7):655-62. DOI: 10.1016/s1074-5521(03)00145-5. View

Walsh C . Polyketide and nonribosomal peptide antibiotics: modularity and versatility. Science. 2004; 303(5665):1805-10. DOI: 10.1126/science.1094318. View

Murakami H, Ohta A, Ashigai H, Suga H . A highly flexible tRNA acylation method for non-natural polypeptide synthesis. Nat Methods. 2006; 3(5):357-9. DOI: 10.1038/nmeth877. View

Mortimer S, Weeks K . A fast-acting reagent for accurate analysis of RNA secondary and tertiary structure by SHAPE chemistry. J Am Chem Soc. 2007; 129(14):4144-5. DOI: 10.1021/ja0704028. View

10.

Guo J, Wang J, Anderson J, Schultz P . Addition of an alpha-hydroxy acid to the genetic code of bacteria. Angew Chem Int Ed Engl. 2007; 47(4):722-5. DOI: 10.1002/anie.200704074. View

11.

Ohta A, Murakami H, Higashimura E, Suga H . Synthesis of polyester by means of genetic code reprogramming. Chem Biol. 2007; 14(12):1315-22. DOI: 10.1016/j.chembiol.2007.10.015. View

12.

Goto Y, Ohta A, Sako Y, Yamagishi Y, Murakami H, Suga H . Reprogramming the translation initiation for the synthesis of physiologically stable cyclic peptides. ACS Chem Biol. 2008; 3(2):120-9. DOI: 10.1021/cb700233t. View

13.

Subtelny A, Hartman M, Szostak J . Ribosomal synthesis of N-methyl peptides. J Am Chem Soc. 2008; 130(19):6131-6. PMC: 2728122. DOI: 10.1021/ja710016v. View

14.

Goto Y, Murakami H, Suga H . Initiating translation with D-amino acids. RNA. 2008; 14(7):1390-8. PMC: 2441986. DOI: 10.1261/rna.1020708. View

15.

Xiao H, Murakami H, Suga H, Ferre-DAmare A . Structural basis of specific tRNA aminoacylation by a small in vitro selected ribozyme. Nature. 2008; 454(7202):358-61. DOI: 10.1038/nature07033. View

16.

Seebach D, Gardiner J . Beta-peptidic peptidomimetics. Acc Chem Res. 2008; 41(10):1366-75. DOI: 10.1021/ar700263g. View

17.

Saraogi I, Incarvito C, Hamilton A . Controlling curvature in a family of oligoamide alpha-helix mimetics. Angew Chem Int Ed Engl. 2008; 47(50):9691-4. DOI: 10.1002/anie.200803778. View

18.

Montalvo G, Waegele M, Shandler S, Gai F, DeGrado W . Infrared signature and folding dynamics of a helical beta-peptide. J Am Chem Soc. 2010; 132(16):5616-8. PMC: 2862463. DOI: 10.1021/ja100459a. View

19.

Goto Y, Katoh T, Suga H . Flexizymes for genetic code reprogramming. Nat Protoc. 2011; 6(6):779-90. DOI: 10.1038/nprot.2011.331. View

20.

Goto Y, Suga H . Flexizymes as a tRNA acylation tool facilitating genetic code reprogramming. Methods Mol Biol. 2012; 848:465-78. DOI: 10.1007/978-1-61779-545-9_29. View