Synthesis 2022; 54(06): 1551-1565
DOI: 10.1055/a-1675-8208
short review

Mechanistic Investigations on Microbial Type I Terpene Synthases through Site-Directed Mutagenesis

Houchao Xu
,


Abstract

During the past three decades many terpene synthases have been characterised from all kingdoms of life. Enzymes of type I, from bacteria, fungi and protists, commonly exhibit several highly conserved motifs and single residues, and the available crystal structures show a shared α-helical fold, while the overall sequence identity is generally low. Several enzymes have been studied by site-directed mutagenesis, giving valuable insights into terpene synthase catalysis and the intriguing mechanisms of terpene synthases. Some mutants are also preparatively useful and give higher yields than the wild type or a different product that is otherwise difficult to access. The accumulated knowledge obtained from these studies is presented and discussed in this review.

1 Introduction

2 Residues for Substrate Binding and Catalysis

3 Residues with Structural Function

4 Residues Contouring the Active Site Cavity

5 Other Residues

6 Conclusions



Publication History

Received: 14 September 2021

Accepted after revision: 21 October 2021

Accepted Manuscript online:
21 October 2021

Article published online:
15 December 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Gershenzon J, Dudareva N. Nat. Chem. Biol. 2007; 3: 408
  • 2 Schwab W, Fuchs C, Huang F.-C. Eur. J. Lipid Sci. Technol. 2013; 115: 3
  • 3 Dickschat JS. Nat. Prod. Rep. 2016; 33: 87
  • 4 Christianson DW. Chem. Rev. 2017; 117: 11570
  • 5 Wendt KU, Schulz GE. Structure 1998; 6: 127
  • 6 Qu G, Li A, Acevedo-Rocha CG, Sun Z, Reetz MT. Angew. Chem. Int. Ed. 2020; 59: 13204
  • 7 Arnold FH. Angew. Chem. Int. Ed. 2019; 58: 14420
  • 8 Xu J, Cen Y, Singh W, Fan J, Wu L, Lin X, Zhou J, Huang M, Reetz MT, Wu Q. J. Am. Chem. Soc. 2019; 141: 7934
  • 9 Li D, Wu Q, Reetz MT. Methods Enzymol. 2020; 643: 225
  • 10 Aaron JA, Lin X, Cane DE, Christianson DW. Biochemistry 2010; 49: 1787
  • 11 Tarshis LC, Yan M, Poulter DC, Sacchettini JC. Biochemistry 1994; 33: 10871
  • 12 Cane DE, Kang I. Arch. Biochem. Biophys. 2000; 376: 354
  • 13 Rynkiewicz MJ, Cane DE, Christianson DW. Proc. Natl. Acad. Sci. U.S.A. 2001; 98: 13543
  • 14 Baer P, Rabe P, Fischer K, Citron CA, Klapschinski TA, Groll M, Dickschat JS. Angew. Chem. Int. Ed. 2014; 53: 7652
  • 15 Starks CM, Back K, Chappell J, Noel JP. Science 1997; 277: 1815
  • 16 Cane DE, Sohng J.-K, Lamberson CR, Rudnicki SM, Wu Z, Lloyd MD, Oliver JS, Hubbard BR. Biochemistry 1994; 33: 5846
  • 17 Gutta P, Tantillo DJ. J. Am. Chem. Soc. 2006; 128: 6172
  • 18 Zu L, Xu M, Lodewyk MW, Cane DE, Peters RJ, Tantillo DJ. J. Am. Chem. Soc. 2012; 134: 11369
  • 19 Seemann M, Zhai G, Umezawa K, Cane DE. J. Am. Chem. Soc. 1999; 121: 591
  • 20 Seemann M, Zhai G, de Kraker J.-W, Paschall CM, Christianson DW, Cane DE. J. Am. Chem. Soc. 2002; 124: 7681
  • 21 Lin X, Cane DE. J. Am. Chem. Soc. 2009; 131: 6332
  • 22 Baer P, Rabe P, Citron CA, de Oliveira Mann CC, Kaufmann N, Groll M, Dickschat JS. ChemBioChem 2014; 15: 213
  • 23 Jiang J, He X, Cane DE. Nat. Chem. Biol. 2007; 3: 711
  • 24 Felicetti B, Cane DE. J. Am. Chem. Soc. 2004; 126: 7212
  • 25 Cane DE, Xue Q, Fitzsimons BC. Biochemistry 1996; 35: 12369
  • 26 Xu H, Rinkel J, Dickschat JS. Org. Chem. Front. 2021; 8: 1177
  • 27 Xu H, Dickschat JS. Chem. Eur. J. 2020; 26: 17318
  • 28 Hou A, Dickschat JS. Beilstein J. Org. Chem. 2021; 17: 2441
  • 29 Rinkel J, Lauterbach L, Rabe P, Dickschat JS. Angew. Chem. Int. Ed. 2018; 57: 3238
  • 30 Rinkel J, Lauterbach L, Dickschat JS. Angew. Chem. Int. Ed. 2017; 56: 16385
  • 31 Lauterbach L, Rinkel J, Dickschat JS. Angew. Chem. Int. Ed. 2018; 57: 8280
  • 32 Srivastava PL, Escorcia AM, Huynh F, Miller DJ, Allemann RK, van der Kamp MW. ACS Catal. 2021; 11: 1033
  • 33 Cane DE, Shim JH, Xue Q, Fitzsimons BC, Hohn TM. Biochemistry 1995; 34: 2480
  • 34 Xu H, Rinkel J, Chen X, Köllner TG, Chen F, Dickschat JS. Org. Biomol. Chem. 2021; 19: 370
  • 35 Rinkel J, Köllner TG, Chen F, Dickschat JS. Chem. Commun. 2019; 55: 13255
  • 36 Hou A, Goldfuss B, Dickschat JS. Angew. Chem. Int. Ed. 2021; 60: 20781
  • 37 Matos JO, Kumar RP, Ma AC, Patterson M, Krauss IJ, Oprian DD. Biochemistry 2020; 59: 3271
  • 38 Li R, Chou WK. W, Himmelberger JA, Litwin KM, Harris GG, Cane DE, Christianson DW. Biochemistry 2014; 53: 1155
  • 39 Blank PN, Barrow GH, Chou WK. W, Duan L, Cane DE, Christianson DW. Biochemistry 2017; 56: 5798
  • 40 Forcat S, Allemann RK. Org. Biomol. Chem. 2006; 4: 2563
  • 41 Kim S.-Y, Zhao P, Igarashi M, Sawa R, Tomita T, Nishiyama M, Kuzuyama T. Chem. Biol. 2009; 16: 736
  • 42 Meguro A, Motoyoshi Y, Teramoto K, Ueda S, Totsuka Y, Ando Y, Tomita T, Kim S.-Y, Kimura T, Igarashi M, Sawa R, Shinada T, Nishiyama M, Kuzuyama T. Angew. Chem. Int. Ed. 2015; 54: 4353
  • 43 Görner C, Häuslein I, Schrepfer P, Eisenreich W, Brück T. ChemCatChem 2013; 5: 3289
  • 44 Tomita T, Kim S.-Y, Teramoto K, Meguro A, Ozaki T, Yoshida A, Motoyoshi Y, Mori N, Ishigami K, Watanabe H, Nishiyama M, Kuzuyama T. ACS Chem. Biol. 2017; 12: 1621
  • 45 Köksal M, Chou WK. W, Cane DE, Christianson DW. Biochemistry 2012; 51: 3011
  • 46 Deligeorgopoulou A, Taylor SE, Forcat S, Allemann RK. Chem. Commun. 2003; 2162
  • 47 Faraldos JA, Antonczak AK, González V, Fullerton R, Tippmann EM, Allemann RK. J. Am. Chem. Soc. 2011; 133: 13906
  • 48 Burkhardt I, Kreuzenbeck N, Beemelmanns C, Dickschat JS. Org. Biomol. Chem. 2019; 17: 3348
  • 49 Janke R, Görner C, Hirte M, Brück T, Loll B. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2014; 70: 1528
  • 50 Lesburg CA, Zhai G, Cane DE, Christianson DW. Science 1997; 277: 1820
  • 51 Gutta P, Tantillo DJ. J. Am. Chem. Soc. 2006; 128: 6172
  • 52 Zu L, Xu M, Lodewyk MW, Cane DE, Peters RJ, Tantillo DJ. J. Am. Chem. Soc. 2012; 134: 11369
  • 53 Lauterbach L, Goldfuss B, Dickschat JS. Angew. Chem. Int. Ed. 2020; 59: 11943
  • 54 Caruthers JM, Kang I, Rynkiewicz MJ, Cane DE, Christianson DW. J. Biol. Chem. 2000; 275: 25533
  • 55 Forcat S, Allemann RK. Chem. Commun. 2004; 2094
  • 56 Faraldos JA, González V, Senske M, Allemann RK. Org. Biomol. Chem. 2011; 9: 6920
  • 57 Calvert MJ, Ashton PR, Allemann RK. J. Am. Chem. Soc. 2002; 124: 11636
  • 58 Calvert MJ, Taylor SE, Allemann RK. Chem. Commun. 2002; 2384
  • 59 Deligeorgopoulou A, Allemann RK. Biochemistry 2003; 42: 7741
  • 60 Chen M, Chou WK. W, Al-Lami N, Faraldos JA, Allemann RK, Cane DE, Christianson DW. Biochemistry 2016; 55: 2864
  • 61 Lauterbach L, Hou A, Dickschat JS. Chem. Eur. J. 2021; 27: 7923