Synthesis of Metabolic Amino acid Precursors: Tools for Selective Isotope Labeling in Cell-Based Protein Overexpression

Abstract

The rapid development of biomolecular NMR spectroscopy in the last decade(s) has paved the way for novel insights into the structure, dynamic properties, as well as the interaction of proteins. However, NMR data interpretation of large protein complexes is only feasible if the corresponding sample is selectively enriched in NMR active nuclei (¹³C and ¹⁵N) and/or ¹H-depleted by ²H incorporation. One important strategy for selective protein isotope labeling is given by the addition of metabolic amino acid precursor compounds to the growth medium of a protein-overexpressing microorganism. Herein, we highlight the synthetic concepts to access these precursors from commercially available isotope sources.

1 Introduction

2 Aliphatic Residue Precursors

3 Aromatic Residue Precursors

4 Precursors of Other Labeled Residues

5 Conclusions

Key words

isotope labeling - protein NMR - α-keto acids - protein overexpression - amino acid precursors

• References

• 1a Protein NMR Spectroscopy – Principles and Practice . 2nd ed.; Palmer AG. III, Fairbrother WJ, Cavanagh J, Skelton NJ, Rance M. Elsevier Academic Press; San Diego: 2005
• 1b Fundamentals of Protein NMR Spectroscopy . Rule GS, Hitchens TK. Springer; Berlin: 2006
• 1c Protein NMR Spectroscopy: Practical Techniques and Applications . Roberts G, Lian L.-Y. J. Wiley and Sons; Chichester: 2011
• 2a Göbl C, Madl T, Simon B, Sattler M. Prog. Nucl. Magn. Reson. Spectrosc. 2014; 80: 26
• 2b Tugarinov V, Hwang PM, Kay LE. Annu. Rev. Biochem. 2004; 73: 107
• 2c Ohki S, Kainosho M. Prog. Nucl. Magn. Reson. Spectrosc. 2008; 53: 208
• 3 Rosenzweig R, Kay LE. Annu. Rev. Biochem. 2014; 83: 291
• 4 Higman VA, Flinders J, Hiller M, Jehle S, Markovic S, Fiedler S, van Rossum B.-J, Oschkinat H. J. Biomol. NMR 2009; 44: 245
• 5 Wand AJ. Nat. Struct. Biol. 2001; 8: 926
• 6 Hoogstraten CG, Johnson JE. Jr. Concepts Magn. Reson., Part A 2008; 32: 34
• 7 Takahashi H, Shimada I. J. Biomol. NMR 2010; 46: 3
• 8 Sobhanifar S, Reckel S, Junge F, Schwarz D, Kai L, Karbyshev M, Löhr F, Bernhard F, Dötsch V. J. Biomol. NMR 2010; 46: 33
• 9a Kainosho M, Torizawa T, Iwashita Y, Terauchi T, Mei Ono A, Güntert P. Nature (London, U.K.) 2006; 440: 52
• 9b Kainosho M, Güntert P. Q. Rev. Biophys. 2009; 42: 247
• 10 Kerfah R, Plevin MJ, Sounier R, Gans P, Boisbouvier J. Curr. Opin. Struct. Biol. 2015; 32: 113
• 11 Rosen MK, Gardner KH, Willis RC, Parris WE, Pawson T, Kay LE. J. Mol. Biol. 1996; 263: 627
• 12a Gardner KH, Kay LE. J. Am. Chem. Soc. 1997; 119: 7599
• 12b Gardner KH, Zhang X, Gehring K, Kay LE. J. Am. Chem. Soc. 1998; 120: 11738
• 12c Goto NK, Gardner KH, Mueller GA, Willis RC, Kay LE. J. Biomol. NMR 1999; 13: 369
• 13 Gross JD, Gelev VM, Wagner G. J. Biomol. NMR 2003; 25: 235
• 14 Hajduk PJ, Augeri DJ, Mack J, Mendoza R, Yang J, Betz SF, Fesik SW. J. Am. Chem. Soc. 2000; 122: 7898
• 15 Lichtenecker R, Ludwiczek ML, Schmid W, Konrat R. J. Am. Chem. Soc. 2004; 126: 5348
• 16a Miyanoiri Y, Takeda M, Okuma K, Ono AM, Terauchi T, Kainosho M. J. Biomol. NMR 2013; 57: 237
• 16b Mas G, Crublet E, Hamelin O, Gans P, Boisbouvier J. J. Biomol. NMR 2013; 57: 251
• 17a Lichtenecker RJ, Coudevylle N, Konrat R, Schmid W. ChemBioChem 2013; 14: 818
• 17b Lichtenecker RJ, Weinhäupl K, Reuther L, Schörghuber J, Schmid W, Konrat R. J. Biomol. NMR 2013; 57: 205
• 18 Gans P, Hamelin O, Sounier R, Ayala I, Asunción Durá M, Amero CD, Noirclerc-Savoye M, Franzetti B, Plevin MJ, Boisbouvier J. Angew. Chem. Int. Ed. 2010; 49: 1958
• 19 Ayala I, Hamelin O, Amero C, Pessey O, Plevin MJ, Gans P, Boisbouvier J. Chem. Commun. 2012; 48: 1434
• 20 Godoy-Ruiz R, Guo C, Tugarinov V. J. Am. Chem. Soc. 2010; 132: 18340
• 21 Isaacson RL, Simpson PJ, Liu M, Cota E, Zhang X, Freemont P, Matthews S. J. Am. Chem. Soc. 2007; 129: 15428
• 22 Ayala I, Sounier R, Usé N, Gans P, Boisbouvier J. J. Biomol. NMR 2009; 43: 111
• 23 Kerfah R, Plevin MJ, Pessey O, Hamelin O, Gans P, Boisbouvier J. J. Biomol. NMR 2015; 61: 73
• 24a Teilum K, Brath U, Lundström P, Akke M. J. Am. Chem. Soc. 2006; 128: 2506
• 24b Kasinath V, Valentine KG, Wand AJ. J. Am. Chem. Soc. 2013; 135: 9560
• 24c LeMaster DM, Kushlan DM. J. Am. Chem. Soc. 1996; 118: 9255
• 25 Takeda M, Ono AM, Terauchi T, Kainosho M. J. Biomol. NMR 2010; 46: 45
• 26 Lichtenecker RJ, Weinhäupl K, Schmid W, Konrat R. J. Biomol. NMR 2013; 57: 327
• 27 Lichtenecker RJ. Org. Biomol. Chem. 2014; 12: 7551
• 28 Viswanatha V, Hruby VJ. J. Org. Chem. 1979; 44: 2892
• 29a Musliner WJ, Gates JW. J. Am. Chem. Soc. 1966; 88: 4271
• 29b Johnstone RA. W, Price PJ. Tetrahedron 1985; 41: 2493
• 30 Martins A, Lautens M. Org. Lett. 2008; 10: 4351
• 31a Rodriguez-Mias RA, Pellecchia M. J. Am. Chem. Soc. 2003; 125: 2892
• 31b Terragó T, Claasen B, Kichik N, Rodriguez-Mias RA, Gairí M, Giralt E. ChemBioChem 2009; 10: 2736
• 32 Schörghuber J, Sara T, Bisaccia M, Schmid W, Konrat R, Lichtenecker RJ. ChemBioChem 2015; 16: 746
• 33 Sinha K, Jen-Jacobson L, Rule GS. Biochemistry 2011; 50: 10189
• 34 Takeda M, Jee J, Ono AM, Terauchi T, Kainosho M. J. Am. Chem. Soc. 2011; 133: 17420
• 35 Velyvis A, Ruschak AM, Kay LE. PLoS One 2012; 7: e43725
• 36 Gelis I, Bonvin AM. J. J, Keramisanou D, Koukaki M, Gouridis G, Karamanou S, Economou A, Kalodimos CG. Cell 2007; 131: 756
• 37 Fischer M, Kloiber K, Häusler J, Ledolter K, Konrat R, Schmid W. ChemBioChem 2007; 8: 610