The triterpene cyclase protein family: A systematic analysis

Proteins: Structure, Function and Bioinformatics

Volumn 80, Issue 8, 2012, Pages 2009-2019

  Racolta, Silvia ^a   Juhl, P Benjamin ^a   Sirim, Demet ^a   Pleiss, Jürgen ^a  

^a UNIVERSITY OF STUTTGART   (Germany)

Author keywords

Oxidosqualene cyclases; Protein engineering; Protein family database; Sequence structure function relationship; Squalene hopene cyclases

Indexed keywords

ASPARTIC ACID; GLYCINE; LANOSTEROL SYNTHASE; LYASE; PHENYLALANINE; PROLINE; PROTEIN SHC; THREONINE; TRITERPENE CYCLASE; TRYPTOPHAN; TYROSINE; UNCLASSIFIED DRUG;

ADIANTUM; AJELLOMYCES; ALICYCLOBACILLUS ACIDOCALDARIUS; ARABIDOPSIS; ARTICLE; ASPERGILLUS; BIRCH; BLACK CUMIN; BRADYRHIZOBIUM; CEPHALOSPORIUM; CRYSTAL STRUCTURE; DRYOPTERIS; FRANKIA; LOTUS JAPONICUS; NONHUMAN; PHYLOGENY; PNEUMOCYSTIS CARINII; PRIORITY JOURNAL; PROTEIN DATABASE; PROTEIN FUNCTION; PROTEIN SECONDARY STRUCTURE; RAT; RICINUS COMMUNIS; SACCHAROMYCES CEREVISIAE; SEQUENCE ALIGNMENT; STREPTOMYCES; TRYPANOSOMA BRUCEI; ZYMOMONAS MOBILIS;

AMINO ACID SEQUENCE; ANIMALS; BACTERIA; DATABASES, PROTEIN; HUMANS; INTERNET; INTRAMOLECULAR TRANSFERASES; PHYLOGENY; STRUCTURAL HOMOLOGY, PROTEIN; TRITERPENES;

EID: 84863784511     PISSN: 08873585     EISSN: 10970134     Source Type: Journal    
DOI: 10.1002/prot.24089     Document Type: Article

References (92)

1. Christianson DW. Structural biology and chemistry of the terpenoid cyclases. Chem Rev 2006; 106: 3412-3442.
2. Wendt KU, Schulz GE. Isoprenoid biosynthesis: manifold chemistry catalyzed by similar enzymes. Structure 1998; 6: 127-133.
3. Frickey T, Kannenberg E. Phylogenetic analysis of the triterpene cyclase protein family in prokaryotes and eukaryotes suggests bidirectional lateral gene transfer. Environ Microbiol 2009; 11: 1224-1241.
4. Wendt KU, Poralla K, Schulz GE. Structure and function of a squalene cyclase. Science 1997; 277: 1811-1815.
5. Thoma R, Schulz-Gasch T, D'Arcy B, Benz J, Aebi J, Dehmlow H, Hennig M, Stihle M, Ruf A. Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase. Nature 2004; 432: 118-122.
6. Abe I. Enzymatic synthesis of cyclic triterpenes. Nat Prod Rep 2007; 24: 1311-1331.
7. Siedenburg G, Jendrossek D. Squalene-hopene cyclases. Appl Environ Microbiol 2011; 77: 3905-3915.
8. Poralla K. The possible role of a repetitive amino-acid motif in evolution of triterpenoid cyclases. Bioorganic Med Chem Lett 1994; 4: 285-290.
9. Poralla K, Hewelt A, Prestwich GD, Abe I, Reipen I, Sprenger G. A specific amino acid repeat in squalene and oxidosqualene cyclases. Trends Biochem Sci 1994; 19: 157-158.
10. Hoshino T, Kumai Y, Kudo I, Nakano S, Ohashi S. Enzymatic cyclization reactions of geraniol, farnesol and geranylgeraniol, and those of truncated squalene analogs having C20 and C25 by recombinant squalene cyclase. Org Biomol Chem 2004; 2: 2650-2657.
11. Ochs D, Kaletta C, Entian KD, Becksickinger A, Poralla K. Cloning, expression, and sequencing of squalene-hopene cyclase, a key enzyme in triterpenoid metabolism. J Bacteriol 1992; 174: 298-302.
12. Wisotzkey JD, Jurtshuk P, Fox GE, Deinhard G, Poralla K. Comparative sequence analyses on the 16s ribosomal-Rna (Rdna) of Bacillus-Acidocaldarius, Bacillus-Acidoterrestris, and Bacillus-Cycloheptanicus and proposal for creation of a new genus, Alicyclobacillus Gen-Nov. Int J Syst Bacteriol 1992; 42: 263-269.
13. Perzl M, Reipen IG, Schmitz S, Poralla K, Sahm H, Sprenger GA, Kannenberg EL. Cloning of conserved genes from Zymomonas mobilis and Bradyrhizobium japonicum that function in the biosynthesis of hopanoid lipids. Biochimica Et Biophysica Acta-Lipids Lipid Metabolism 1998; 1393: 108-118.
14. Tippelt A, Jahnke L, Poralla K. Squalene-hopene cyclase from Methylococcus capsulatus (Bath): a bacterium producing hopanoids and steroids. Biochimica Et Biophysica Acta-Lipids Lipid Metabolism 1998; 1391: 223-232.
15. Reipen IG, Poralla K, Sahm H, Sprenger GA. Zymomonas-mobilis squalene-hopene cyclase gene (Shc)-cloning, DNA-sequence analysis, and expression in Escherichia-Coli. Microbiol-Sgm 1995; 141: 155-161.
16. Wu TK, Chang CH, Liu YT, Wang TT. Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase: a chemistry-biology interdisciplinary study of the protein's structure-function-reaction mechanism relationships. Chem Rec 2008; 8: 302-325.
17. Scholz M, Lipinski M, Leupold M, Luftmann H, Harig L, Ofir R, Fischer R, Prufer D, Muller KJ. Methyl jasmonate induced accumulation of kalopanaxsaponin I in Nigella sativa. Phytochemistry 2009; 70: 517-522.
18. Segura MJR, Jackson BE, Matsuda SPT. Mutagenesis approaches to deduce structure-function relationships in terpene synthases. Nat Product Reports 2003; 20: 304-317.
19. Cravotto G, Balliano G, Robaldo B, Oliaro-Bosso S, Chimichi S, Boccalini M. Farnesyloxycoumarins, a new class of squalene-hopene cyclase inhibitors. Bioorg Med Chem Lett 2004; 14: 1931-1934.
20. Sato T, Hoshino T. Functional analysis of the DXDDTA motif in squalene-hopene cyclase by site-directed mutagenesis experiments: initiation site of the polycyclization reaction and stabilization site of the carbocation intermediate of the initially cyclized A-ring. Biosci Biotechnol Biochem 1999; 63: 2189-2198.
21. Abe I, Prestwich GD. Molecular cloning, characterization, and functional expression of rat oxidosqualene cyclase cDNA. Proc Natl Acad Sci USA 1995; 92: 9274-9278.
22. Corey EJ, Cheng HM, Baker CH, Matsuda SPT, Li D, Song XL. Studies on the substrate binding segments and catalytic action of lanosterol synthase. Affinity labeling with carbocations derived from mechanism-based analogs of 2, 3-oxidosqualene and site-directed mutagenesis probes. J Am Chem Soc 1997; 119: 1289-1296.
23. Fischer M, Pleiss J. The Lipase Engineering Database: a navigation and analysis tool for protein families. Nucleic Acids Res 2003; 31: 319-321.
24. Knoll M, Pleiss J. The medium-chain dehydrogenase/reductase engineering database: a systematic analysis of a diverse protein family to understand sequence-structure-function relationship. Protein Sci 2008; 17: 1689-1697.
25. Sirim D, Wagner F, Lisitsa A, Pleiss J. The Cytochrome P450 Engineering Database: integration of biochemical properties. BMC Biochem 2009; 10: 27.
26. Seifert A, Pleiss J. Identification of selectivity-determining residues in cytochrome P450 monooxygenases: a systematic analysis of the substrate recognition site 5. Proteins 2009; 74: 1028-1035.
27. Seifert A, Vomund S, Grohmann K, Kriening S, Urlacher VB, Laschat S, Pleiss J. Rational design of a minimal and highly enriched CYP102A1 mutant library with improved regio-, stereo- and chemoselectivity. Chembiochem 2009; 10: 853-861.
28. Fischer M, Thai QK, Grieb M, Pleiss J. DWARF-a data warehouse system for analyzing protein families. BMC Bioinformatics 2006; 7: 495.
29. Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997; 25: 3389-3402.
30. Berman HM, Battistuz T, Bhat TN, Bluhm WF, Bourne PE, Burkhardt K, Feng Z, Gilliland GL, Iype L, Jain S, Fagan P, Marvin J, Padilla D, Ravichandran V, Schneider B, Thanki N, Weissig H, Westbrook JD, Zardecki C. The Protein Data Bank. Acta Crystallogr D Biol Crystallogr 2002; 58(PART 6 NO 1): 899-907.
31. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 1994; 22: 4673-4680.
32. Felsenstein J. PHYLIP (Phylogeny Inference Package) version 3.6: Department of Genome Sciences, University of Washington, Seattle; 2005.
33. Jones DT, Taylor WR, Thornton JM. The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci 1992; 8: 275-282.
34. Kabsch W, Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 1983; 22: 2577-2637.
35. Rice P, Longden I, Bleasby A. EMBOSS: the European Molecular Biology Open Software Suite. Trends Genet 2000; 16: 276-277.
36. Reinert DJ, Balliano G, Schulz GE. Conversion of squalene to the pentacarbocyclic hopene. Chem Biol 2004; 11: 121-126.
37. Delano WL. The PyMOL molecular graphics system. San Carlos, CA: DeLano Scientific; 2002.
38. Sobolev V, Sorokine A, Prilusky J, Abola EE, Edelman M. Automated analysis of interatomic contacts in proteins. Bioinformatics 1999; 15: 327-332.
39. Giraud E, Moulin L, Vallenet D, Barbe V, Cytryn E, Avarre JC, Jaubert M, Simon D, Cartieaux F, Prin Y, Bena G, Hannibal L, Fardoux J, Kojadinovic M, Vuillet L, Lajus A, Cruveiller S, Rouy Z, Mangenot S, Segurens B, Dossat C, Franck WL, Chang WS, Saunders E, Bruce D, Richardson P, Normand P, Dreyfus B, Pignol D, Stacey G, Emerich D, Vermeglio A, Medigue C, Sadowsky M. Legumes symbioses: absence of Nod genes in photosynthetic bradyrhizobia. Science 2007; 316: 1307-1312.
40. Yang S, Pappas KM, Hauser LJ, Land ML, Chen GL, Hurst GB, Pan C, Kouvelis VN, Typas MA, Pelletier DA, Klingeman DM, Chang YJ, Samatova NF, Brown SD. Improved genome annotation for Zymomonas mobilis. Nat Biotechnol 2009; 27: 893-894.
41. Shinozaki J, Shibuya M, Masuda K, Ebizuka Y. Squalene cyclase and oxidosqualene cyclase from a fern. FEBS Lett 2008; 582: 310-318.
42. Shinozaki J, Shibuya M, Masuda K, Ebizuka Y. Dammaradiene synthase, a squalene cyclase, from Dryopteris crassirhizoma Nakai. Phytochemistry 2008; 69: 2559-2564.
43. Buckner FS, Nguyen LN, Joubert BM, Matsuda SP. Cloning and heterologous expression of the Trypanosoma brucei lanosterol synthase gene. Mol Biochem Parasitol 2000; 110: 399-403.
44. Abe I, Naito K, Takagi Y, Noguchi H. Molecular cloning, expression, and site-directed mutations of oxidosqualene cyclase from Cephalosporium caerulens. Biochim Biophys Acta 2001; 1522: 67-73.
45. Milla P, Viola F, Oliaro Bosso S, Rocco F, Cattel L, Joubert BM, LeClair RJ, Matsuda SP, Balliano G. Subcellular localization of oxidosqualene cyclases from Arabidopsis thaliana, Trypanosoma cruzi, and Pneumocystis carinii expressed in yeast. Lipids 2002; 37: 1171-1176.
46. Corey EJ, Matsuda SP, Bartel B. Molecular cloning, characterization, and overexpression of ERG7, the Saccharomyces cerevisiae gene encoding lanosterol synthase. Proc Natl Acad Sci USA 1994; 91: 2211-2215.
47. Shi Z, Buntel CJ, Griffin JH. Isolation and characterization of the gene encoding 2, 3-oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae. Proc Natl Acad Sci USA 1994; 91: 7370-7374.
48. Godio RP, Martin JF. Modified oxidosqualene cyclases in the formation of bioactive secondary metabolites: biosynthesis of the antitumor clavaric acid. Fungal Genet Biol 2009; 46: 232-242.
49. Kusano M, Shibuya M, Sankawa U, Ebizuka Y. Molecular cloning of cDNA encoding rat 2, 3-oxidosqualene: lanosterol cyclase. Biol Pharm Bull 1995; 18: 195-197.
50. Corey EJ, Matsuda SP, Bartel B. Isolation of an Arabidopsis thaliana gene encoding cycloartenol synthase by functional expression in a yeast mutant lacking lanosterol synthase by the use of a chromatographic screen. Proc Natl Acad Sci USA 1993; 90: 11628-11632.
51. Zhang H, Shibuya M, Yokota S, Ebizuka Y. Oxidosqualene cyclases from cell suspension cultures of Betula platyphylla var. japonica: molecular evolution of oxidosqualene cyclases in higher plants. Biol Pharm Bull 2003; 26: 642-650.
52. Guhling O, Hobl B, Yeats T, Jetter R. Cloning and characterization of a lupeol synthase involved in the synthesis of epicuticular wax crystals on stem and hypocotyl surfaces of Ricinus communis. Arch Biochem Biophys 2006; 448(1-2): 60-72.
53. Kolesnikova MD, Xiong QB, Lodeiro S, Hua L, Matsuda SPT. Lanosterol biosynthesis in plants. Arch Biochem Biophys 2006; 447: 87-95.
54. Sawai S, Akashi T, Sakurai N, Suzuki H, Shibata D, Ayabe SI, Aoki T. Plant lanosterol synthase: Divergence of the sterol and triterpene biosynthetic pathways in eukaryotes. Plant Cell Physiol 2006; 47: 673-677.
55. Xiang T, Shibuya M, Katsube Y, Tsutsumi T, Otsuka M, Zhang H, Masuda K, Ebizuka Y. A new triterpene synthase from Arabidopsis thaliana produces a tricyclic triterpene with two hydroxyl groups. Org Lett 2006; 8: 2835-2838.
56. Herrera JB, Bartel B, Wilson WK, Matsuda SP. Cloning and characterization of the Arabidopsis thaliana lupeol synthase gene. Phytochemistry 1998; 49: 1905-1911.
57. Hoshino T, Sato T. Squalene-hopene cyclase: catalytic mechanism and substrate recognition. Chem Commun (Camb) 2002: 291-301.
58. Sato T, Kouda M, Hoshino T. Site-directed mutagenesis experiments on the putative deprotonation site of squalene-hopene cyclase from Alicyclobacillus acidocaldarius. Biosci Biotechnol Biochem 2004; 68: 728-738.
59. Sato T, Hoshino T. Catalytic function of the residues of phenylalanine and tyrosine conserved in squalene-hopene cyclases. Biosci Biotechnol Biochem 2001; 65: 2233-2242.
60. Sato T, Hoshino T. Kinetic studies on the function of all the conserved tryptophans involved inside and outside the QW motifs of squalene-hopene cyclase: stabilizing effect of the protein structure against thermal denaturation. Biosci Biotechnol Biochem 1999; 63: 1171-1180.
61. Hoshino T, Abe T, Kouda M. Unnatural natural triterpenes produced by altering isoleucine into alanine at position 261 in hopene synthase and the importance of having the appropriate bulk size at this position for directing the stereochemical destiny during the polycyclization cascade. Chem Commun 2000: 441-442.
62. Sato T, Kanai Y, Hoshino T. Overexpression of squalene-hopene cyclase by the pET vector in Escherichia coli and first identification of tryptophan and aspartic acid residues inside the QW motif as active sites. Biosci Biotechnol Biochem 1998; 62: 407-411.
63. Morikubo N, Fukuda Y, Ohtake K, Shinya N, Kiga D, Sakamoto K, Asanuma M, Hirota H, Yokoyama S, Hoshino T. Cation-pi interaction in the polyolefin cyclization cascade uncovered by incorporating unnatural amino acids into the catalytic sites of squalene cyclase. J Am Chem Soc 2006; 128: 13184-13194.
64. Feil C, Sussmuth R, Jung G, Poralla K. Site-directed mutagenesis of putative active-site residues in squalene-hopene cyclase. Eur J Biochem 1996; 242: 51-55.
65. Ceruti M, Balliano G, Rocco F, Lenhart A, Schulz GE, Castelli F, Milla P. Synthesis and biological activity of new iodoacetamide derivatives on mutants of squalene-hopene cyclase. Lipids 2005; 40: 729-735.
66. Milla P, Lenhart A, Grosa G, Viola F, Weihofen WA, Schulz GE, Balliano G. Thiol-modifying inhibitors for understanding squalene cyclase function. Eur J Biochem 2002; 269: 2108-2116.
67. Dang T, Prestwich GD. Site-directed mutagenesis of squalene-hopene cyclase: altered substrate specificity and product distribution. Chem Biol 2000; 7: 643-649.
68. Sato T, Sasahara S, Yamakami T, Hoshino T. Functional analyses of Tyr420 and Leu607 of Alicyclobacillus acidocaldarius squalene-hopene cyclase. Neoachillapentaene, a novel triterpene with the 1, 5, 6-trimethylcyclohexene moiety produced through folding of the constrained boat structure. Biosci Biotechnol Biochem 2002; 66: 1660-1670.
69. Full C. Bicyclic triterpenes as new main products of squalene-hopene cyclase by mutation at conserved tyrosine residues. FEBS Lett 2001; 509: 361-364.
70. Hoshino T, Kouda M, Abe T, Ohashi S. New cyclization mechanism for squalene: a ring-expansion step for the five-membered C-ring intermediate in hopene biosynthesis. Biosci Biotechnol Biochem 1999; 63: 2038-2041.
71. Full C, Poralla K. Conserved tyr residues determine functions of Alicyclobacillus acidocaldarius squalene-hopene cyclase. FEMS Microbiol Lett 2000; 183: 221-224.
72. Corey EJ, Matsuda SP, Baker CH, Ting AY, Cheng H. Molecular cloning of a Schizosaccharomyces pombe cDNA encoding lanosterol synthase and investigation of conserved tryptophan residues. Biochem Biophys Res Commun 1996; 219: 327-331.
73. Wu TK, Yu MT, Liu YT, Chang CH, Wang HJ, Diau EW. Tryptophan 232 within oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae influences rearrangement and deprotonation but not cyclization reactions. Org Lett 2006; 8: 1319-1322.
74. Meyer MM, Segura MJ, Wilson WK, Matsuda SP. Oxidosqualene cyclase residues that promote formation of cycloartenol, lanosterol, and parkeol. Angew Chem Int Ed Engl 2000; 39: 4090-4092.
75. Wu TK, Liu YT, Chiu FH, Chang CH. Phenylalanine 445 within oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae influences C-Ring cyclization and deprotonation reactions. Org Lett 2006; 8: 4691-4694.
76. Joubert BM, Hua L, Matsuda SP. Steric bulk at position 454 in Saccharomyces cerevisiae lanosterol synthase influences B-ring formation but not deprotonation. Org Lett 2000; 2: 339-341.
77. Wu TK, Chang CH. Enzymatic formation of multiple triterpenes by mutation of tyrosine 510 of the oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae. Chembiochem 2004; 5: 1712-1715.
78. Oliaro-Bosso S, Schulz-Gasch T, Balliano G, Viola F. Access of the substrate to the active site of yeast oxidosqualene cyclase: an inhibition and site-directed mutagenesis approach. Chembiochem 2005; 6: 2221-2228.
79. Lodeiro S, Wilson WK, Shan H, Matsuda SP. A putative precursor of isomalabaricane triterpenoids from lanosterol synthase mutants. Org Lett 2006; 8: 439-442.
80. Wu TK, Chang CH, Wen HY, Liu YT, Li WH, Wang TT, Shie WS. Alteration of the substrate's prefolded conformation and cyclization stereochemistry of oxidosqualene-lanosterol cyclase of Saccharomyces cerevisiae by substitution at phenylalanine 699. Org Lett 2010; 12: 500-503.
81. Wu TK, Chang YC, Liu YT, Chang CH, Wen HY, Li WH, Shie WS. Mutation of isoleucine 705 of the oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae affects lanosterol's C/D-ring cyclization and 17alpha/beta-exocyclic side chain stereochemistry. Org Biomol Chem 2011; 9: 1092-1097.
82. Wu TK, Wang TT, Chang CH, Liu YT, Shie WS. Importance of Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase tyrosine 707 residue for chair-boat bicyclic ring formation and deprotonation reactions. Org Lett 2008; 10: 4959-4962.
83. Lodeiro S, Schulz-Gasch T, Matsuda SP. Enzyme redesign: two mutations cooperate to convert cycloartenol synthase into an accurate lanosterol synthase. J Am Chem Soc 2005; 127: 14132-14133.
84. Wu TK, Griffin JH. Conversion of a plant oxidosqualene-cycloartenol synthase to an oxidosqualene-lanosterol cyclase by random mutagenesis. Biochemistry 2002; 41: 8238-8244.
85. Meyer MM, Xu R, Matsuda SP. Directed evolution to generate cycloartenol synthase mutants that produce lanosterol. Org Lett 2002; 4: 1395-1398.
86. Segura MJ, Lodeiro S, Meyer MM, Patel AJ, Matsuda SP. Directed evolution experiments reveal mutations at cycloartenol synthase residue His477 that dramatically alter catalysis. Org Lett 2002; 4: 4459-4462.
87. Kimura M, Kushiro T, Shibuya M, Ebizuka Y, Abe I. Protostadienol synthase from Aspergillus fumigatus: functional conversion into lanosterol synthase. Biochem Biophys Res Commun 2009; 391: 899-902.
88. Siendenburg G, Jendroseek D, Breuer M, Juhl B, Pleiss J, Seitz M, Klebensberger J, Hauer B, Activation-independent cyclization of monoter penoids. Appl Envison Microbiol 2012; 78: 1055-1062.
89. Reipen IG, Poralla K, Sahm H, Sprenger GA. Zymomonas mobilis squalene-hopene cyclase gene (shc): cloning, DNA sequence analysis, and expression in Escherichia coli. Microbiology 1995; 141(PART 1): 155-161.
90. Douka E, Koukkou AI, Drainas C, Grosdemange-Billiard C, Rohmer M. Structural diversity of the triterpenic hydrocarbons from the bacterium Zymomonas mobilis: the signature of defective squalene cyclization by the squalene/hopene cyclase. Fems Microbiol Lett 2001; 199: 247-251.
91. Wu T-K, Li W-H, Chang C-H, Wen H-Y, Liu Y-T, Chang Y-C. Differential stereocontrolled formation of tricyclic triterpenes by mutation of tyrosine 99 of the oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae. Eur J Organ Chem 2009; 2009: 5731-5737.
92. Wu TK, Liu YT, Chang CH, Yu MT, Wang HJ. Site-saturated mutagenesis of histidine 234 of Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase demonstrates dual functions in cyclization and rearrangement reactions. J Am Chem Soc 2006; 128: 6414-6419.