Gene discovery of modular diterpene metabolism in nonmodel systems

Plant Physiology

Volumn 162, Issue 2, 2013, Pages 1073-1091

  Zerbe, Philipp ^a   Hamberger, Björn ^a,b   Yuen, Macaire M S ^a   Chiang, Angela ^a   Sandhu, Harpreet K ^a   Madilao, Lina L ^a   Nguyen, Anh ^a   Hamberger, Britta ^a,b   Bach, Søren Spanner ^b   Bohlmann, Jörg ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450; DITERPENE; TRANSCRIPTOME; VEGETABLE PROTEIN;

ARTICLE; DATA MINING; GENETIC DATABASE; GENETICS; METABOLISM; METHODOLOGY; MOLECULAR BIOLOGY; MOLECULAR CLONING; MOLECULAR EVOLUTION; MOLECULAR GENETICS; PHYLOGENY; PLANT;

CLONING, MOLECULAR; CYTOCHROME P-450 ENZYME SYSTEM; DATA MINING; DATABASES, GENETIC; DITERPENES; EVOLUTION, MOLECULAR; MOLECULAR BIOLOGY; MOLECULAR SEQUENCE DATA; PHYLOGENY; PLANT PROTEINS; PLANTS; TRANSCRIPTOME;

EID: 84878460164     PISSN: 00320889     EISSN: 15322548     Source Type: Journal    
DOI: 10.1104/pp.113.218347     Document Type: Article

References (106)

1. Ajikumar PK, Xiao WH, Tyo KE, Wang Y, Simeon F, Leonard E, Mucha O, Phon TH, Pfeifer B, Stephanopoulos G (2010) Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science 330: 70-74
2. Alasbahi RH, Melzig MF (2010a) Plectranthus barbatus: a review of phy-tochemistry, ethnobotanical uses and pharmacology - Part 1. Planta Med 76: 653-661
3. Alasbahi RH, Melzig MF (2010b) Plectranthus barbatus: a review of phy-tochemistry, ethnobotanical uses and pharmacology - Part 2. Planta Med 76: 753-765
4. Anisimova M, Gil M, Dufayard JF, Dessimoz C, Gascuel O (2011) Survey of branch support methods demonstrates accuracy, power, and robustness of fast likelihood-based approximation schemes. Syst Biol 60: 685-699
5. Baldwin IT (2010) Plant volatiles. Curr Biol 20: R392-R397
6. Bohlmann J, Meyer-Gauen G, Croteau R (1998a) Plant terpenoid syn-thases: molecular biology and phylogenetic analysis. Proc Natl Acad Sci USA 95: 4126-4133
7. Bohlmann J, Crock J, Jetter R, Croteau R (1998b) cDNA cloning, characterization, and functional expression of wound-inducible (E)-a-bisabolene synthase from grand fir (Abies grandis). Proc Natl Acad Sci USA 95: 6756-6761
8. Bohlmann J, Keeling CI (2008) Terpenoid biomaterials. Plant J 54: 656-669
9. Brinker AM, Ma J, Lipsky PE, Raskin I (2007) Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae). Phytochemistry 68: 732-766
10. Caniard A, Zerbe P, Legrand S, Cohade A, Valot N, Magnard JL, Bohlmann J, Legendre L (2012) Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture. BMC Plant Biol 12: 119
11. Castresana J (2000) Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol 17: 540-552
12. Chen F, Tholl D, Bohlmann J, Pichersky E (2011) The family of terpene synthases in plants: a mid-size family of genes for specialized metabolism that is highly diversified throughout the kingdom. Plant J 66: 212-229
13. Chiu P, Leung LT, Ko BCB (2010) Pseudolaric acids: isolation, bioactivity and synthetic studies. Nat Prod Rep 27: 1066-1083
14. Criswell J, Potter K, Shephard F, Beale MH, Peters RJ (2012) A single residue change leads to a hydroxylated product from the class II di-terpene cyclization catalyzed by abietadiene synthase. Org Lett 14: 5828-5831
15. Davis EM, Croteau R (2000) Cyclization enzymes in the biosynthesis of monoterpenes, sesquiterpenes, and diterpenes. Top Curr Chem 209: 53-95
16. De Smet R, Adams KL, Vandepoele K, Van Montagu MC, Maere S, Van de Peer Y (2013) Convergent gene loss following gene and genome duplications creates single-copy families in flowering plants. Proc Natl Acad Sci USA 110: 2898-2903
17. Dudareva N, Cseke L, Blanc VM, Pichersky E (1996) Evolution of floral scent in Clarkia: novel patterns of S-linalool synthase gene expression in the C. breweri flower. Plant Cell 8: 1137-1148
18. Ennajdaoui H, Vachon G, Giacalone C, Besse I, Sallaud C, Herzog M, Tissier A (2010) Trichome specific expression of the tobacco (Nicotiana sylvestris) cembratrien-ol synthase genes is controlled by both activating and repressing cis-regions. Plant Mol Biol 73: 673-685
19. Facchini PJ, Bohlmann J, Covello PS, De Luca V, Mahadevan R, Page JE, Ro DK, Sensen CW, Storms R, Martin VJ (2012) Synthetic biosystems for the production of high-value plant metabolites. Trends Biotechnol 30: 127-131
20. Falara V, Pichersky E, Kanellis AK (2010) A copal-8-ol diphosphate syn-thase from the angiosperm Cistus creticus subsp. creticus is a putative key enzyme for the formation of pharmacologically active, oxygen-containing labdane-type diterpenes. Plant Physiol 154: 301-310
21. Feyereisen R (2011) Arthropod CYPomes illustrate the tempo and mode in P450 evolution. Biochim Biophys Acta 1814: 19-28
22. Gao W, Hillwig ML, Huang L, Cui G, Wang X, Kong J, Yang B, Peters RJ (2009) A functional genomics approach to tanshinone biosynthesis provides stereochemical insights. Org Lett 11: 5170-5173
23. Gao Y, Honzatko RB, Peters RJ (2012) Terpenoid synthase structures: a so far incomplete view of complex catalysis. Nat Prod Rep 29: 1153-1175
24. Goyal SK, Samsher, Goyal RK (2010) Stevia (Stevia rebaudiana) a bio-sweetener: a review. Int J Food Sci Nutr 61: 1-10
25. Grabherr MG, Haas BJ, Yassour M, Levin JZ, Thompson DA, Amit I, Adiconis X, Fan L, Raychowdhury R, Zeng Q, et al (2011) Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat Biotechnol 29: 644-652
26. Guerra-Bubb J, Croteau R, Williams RM (2012) The early stages of taxol biosynthesis: an interim report on the synthesis and identification of early pathway metabolites. Nat Prod Rep 29: 683-696
27. Hall DE, Zerbe P, Jancsik S, Quesada AL, Dullat H, Madilao LL, Yuen M, Bohlmann J (2013) Evolution of conifer diterpene synthases: diterpene resin acid biosynthesis in lodgepole pine and jack pine involves mono-functional and bifunctional diterpene synthases. Plant Physiol 161: 600-616
28. Hamberger B, Ohnishi T, Hamberger B, Séguin A, Bohlmann J (2011) Evolution of diterpene metabolism: Sitka spruce CYP720B4 catalyzes multiple oxidations in resin acid biosynthesis of conifer defense against insects. Plant Physiol 157: 1677-1695
29. Hamberger B, Bak S (2013) Plant P450s as versatile drivers for evolution of species-specific chemical diversity. Philos Trans R Soc Lond B Biol Sci 368: 20120426
30. Harris LJ, Saparno A, Johnston A, Prisic S, Xu M, Allard S, Kathiresan A, Ouellet T, Peters RJ (2005) The maize An2 gene is induced by Fusarium attack and encodes an ent-copalyl diphosphate synthase. Plant Mol Biol 59: 881-894
31. Hayashi K-I, Kawaide H, Notomi M, Sakigi Y, Matsuo A, Nozaki H (2006) Identification and functional analysis of bifunctional ent-kaurene syn-thase from the moss Physcomitrella patens. FEBS Lett 580: 6175-6181
32. Heiling S, Schuman MC, Schoettner M, Mukerjee P, Berger B, Schneider B, Jassbi AR, Baldwin IT (2010) Jasmonate and ppHsystemin regulate key malonylation steps in the biosynthesis of 17-hydroxygeranyllinalool diterpene glycosides, an abundant and effective direct defense against herbivores in Nicotiana attenuata. Plant Cell 22: 273-292
33. Herde M, Gärtner K, Köllner TG, Fode B, Boland W, Gershenzon J, Gatz C, Tholl D (2008) Identification and regulation of TPS04/GES, an Arab- idopsis geranyllinalool synthase catalyzing the first step in the forma tion of the insect-induced volatile C16-homoterpene TMTT. Plant Cell 20: 1152-1168
34. Hezari M, Lewis NG, Croteau R (1995) Purification and characterization of taxa-4(5),11(12)-diene synthase from Pacific yew (Taxus brevifolia) that catalyzes the first committed step of taxol biosynthesis. Arch Biochem Biophys 322: 437-444
35. Higashi Y, Saito K (2013) Network analysis for gene discovery in plant specialized metabolism. Plant Cell Environ (in press)
36. Hillwig ML, Xu M, Toyomasu T, Tiernan MS, Wei G, Cui G, Huang L, Peters RJ (2011) Domain loss has independently occurred multiple times in plant terpene synthase evolution. Plant J 68: 1051-1060
37. Jassbi AR, Gase K, Hettenhausen C, Schmidt A, Baldwin IT (2008) Silencing geranylgeranyl diphosphate synthase in Nicotiana attenuata dramatically impairs resistance to tobacco hornworm. Plant Physiol 146: 974-986
38. Jennewein S, Croteau R (2001) Taxol: biosynthesis, molecular genetics, and biotechnological applications. Appl Microbiol Biotechnol 57: 13-19
39. Jennewein S, Long RM, Williams RM, Croteau R (2004) Cytochrome p450 taxadiene 5alpha-hydroxylase, a mechanistically unusual monooxygenase catalyzing the first oxygenation step of taxol biosynthesis. Chem Biol 11: 379-387
40. Jiang M, Stephanopoulos G, Pfeifer BA (2012) Downstream reactions and engineering in the microbially reconstituted pathway for Taxol. Appl Microbiol Biotechnol 94: 841-849
41. Keeling CI, Bohlmann J (2006) Genes, enzymes and chemicals of terpenoid diversity in the constitutive and induced defence of conifers against insects and pathogens. New Phytol 170: 657-675
42. Keeling CI, Weisshaar S, Lin RPC, Bohlmann J (2008) Functional plasticity of paralogous diterpene synthases involved in conifer defense. Proc Natl Acad Sci USA 105: 1085-1090
43. Keeling CI, Dullat HK, Yuen M, Ralph SG, Jancsik S, Bohlmann J (2010) Identification and functional characterization of monofunc-tional ent-copalyl diphosphate and ent-kaurene synthases in white spruce reveal different patterns for diterpene synthase evolution for primary and secondary metabolism in gymnosperms. Plant Physiol 152: 1197-1208
44. Keeling CI, Weisshaar S, Ralph SG, Jancsik S, Hamberger B, Dullat HK, Bohlmann J (2011a) Transcriptome mining, functional characterization, and phylogeny of a large terpene synthase gene family in spruce (Picea spp). BMC Plant Biol 11: 11-43
45. Keeling CI, Madilao LL, Zerbe P, Dullat HK, Bohlmann J (2011b) The primary diterpene synthase products of Picea abies levopimaradiene/ abietadiene synthase (PaLAS) are epimers of a thermally unstable di-terpenol. J Biol Chem 286: 21145-21153
46. Kirby J, Nishimoto M, Park JG, Withers ST, Nowroozi F, Behrendt D, Rutledge EJ, Fortman JL, Johnson HE, Anderson JV, et al(2010) Cloning of casbene and neocembrene synthases from Euphorbiaceae plants and expression in Saccharomyces cerevisiae. Phytochemistry 71: 1466-1473
47. Köksal M, Jin Y, Coates RM, Croteau R, Christianson DW (2011) Tax-adiene synthase structure and evolution of modular architecture in terpene biosynthesis. Nature 469: 116-120
48. Kolosova N, Miller B, Ralph S, Ellis BE, Douglas C, Ritland K, Bohlmann J (2004) Isolation of high-quality RNA from gymnosperm and angio-sperm trees. Biotechniques 36: 821-824
49. Leonard E, Ajikumar PK, Thayer K, Xiao WH, Mo JD, Tidor B, Stephanopoulos G, Prather KL (2010) Combining metabolic and protein engineering of a terpenoid biosynthetic pathway for overproduction and selectivity control. Proc Natl Acad Sci USA 107: 13654-13659
50. Li CY, Wang EQ, Cheng Y, Bao JK (2011) Oridonin: An active diterpenoid targeting cell cycle arrest, apoptotic and autophagic pathways for cancer therapeutics. Int J Biochem Cell Biol 43: 701-704
51. Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: 1754-1760
52. Li L, Shukla S, Lee A, Garfield SH, Maloney DJ, Ambudkar SV, Yuspa SH (2010) The skin cancer chemotherapeutic agent ingenol-3-angelate (PEP005) is a substrate for the epidermal multidrug transporter (ABCB1) and targets tumor vasculature. Cancer Res 70: 4509-4519
53. López-Jiménez A, García-Caballero M, Medina MA, Quesada AR (2011) Anti-angiogenic properties of carnosol and carnosic acid, two major dietary compounds from rosemary. Eur J Nutr 52: 85-95
54. Ma Y, Yuan L, Wu B, Li X, Chen S, Lu S (2012) Genome-wide identification and characterization of novel genes involved in terpenoid biosynthesis in Salvia miltiorrhiza. J Exp Bot 63: 2809-2823
55. Mafu S, Hillwig ML, Peters RJ (2011) A novel labda-7,13e-dien-15-ol-producing bifunctional diterpene synthase from Selaginella moellendorffii. ChemBioChem 12: 1984-1987
56. Martin DM, Fäldt J, Bohlmann J (2004) Functional characterization of nine Norway spruce TPS genes and evolution of gymnosperm terpene synthases of the TPS-d subfamily. Plant Physiol 135: 1908-1927
57. Martin DM, Aubourg S, Schouwey MB, Daviet L, Schalk M, Toub O, Lund ST, Bohlmann J (2010) Functional annotation, genome organization and phylogeny of the grapevine (Vitis vinifera) terpene synthase gene family based on genome assembly, FLcDNA cloning, and enzyme assays. BMC Plant Biol 10: 226
58. Mau CJ, West CA (1994) Cloning of casbene synthase cDNA: evidence for conserved structural features among terpenoid cyclases in plants. Proc Natl Acad Sci USA 91: 8497-8501
59. McAndrew RP, Peralta-Yahya PP, DeGiovanni A, Pereira JH, Hadi MZ, Keasling JD, Adams PD (2011) Structure of a three-domain sesquiterpene synthase: a prospective target for advanced biofuels production. Structure 19: 1876-1884
60. Meyre-Silva C, Cechinel-Filho V (2010) A review of the chemical and pharmacological aspects of the genus marrubium. Curr Pharm Des 16: 3503-3518
61. Mnonopi N, Levendal RA, Mzilikazi N, Frost CL (2012) Marrubiin, a constituent of Leonotis leonurus, alleviates diabetic symptoms. Phyto-medicine 19: 488-493
62. Morgenstern B (2004) DIALIGN: multiple DNA and protein sequence alignment at BiBiServ. Nucleic Acids Res 32: W33-36
63. Morrone D, Xu M, Fulton DB, Determan MK, Peters RJ (2008) Increasing complexity of a diterpene synthase reaction with a single residue switch. J Am Chem Soc 130: 5400-5401
64. Nelson D, Werck-Reichhart D (2011) A P450-centric view of plant evolution. Plant J 66: 194-211
65. Nørholm MH (2010) A mutant Pfu DNA polymerase designed for advanced uracil-excision DNA engineering. BMC Biotechnol 10: 21
66. Nour-Eldin HH, Hansen BG, Nørholm MH, Jensen JK, Halkier B A (2006) Advancing uracil-excision based cloning towards an ideal technique for cloning PCR fragments. Nucleic Acids Res 34: e122
67. Parra G, Bradnam K, Korf I (2007) CEGMA: a pipeline to accurately annotate core genes in eukaryotic genomes. Bioinformatics 23: 1061-1067
68. Peters RJ, Flory JE, Jetter R, Ravn MM, Lee HJ, Coates RM, Croteau RB (2000) Abietadiene synthase from grand fir (Abies grandis): characterization and mechanism of action of the "pseudomature" recombinant enzyme. Biochemistry 39: 15592-15602
69. Peters RJ (2006) Uncovering the complex metabolic network underlying diterpenoid phytoalexin biosynthesis in rice and other cereal crop plants. Phytochemistry 67: 2307-2317
70. Peters RJ (2010) Two rings in them all: the labdane-related diterpenoids. Nat Prod Rep 27: 1521-1530
71. Pichersky E, Lewinsohn E (2011) Convergent evolution in plant specialized metabolism. Annu Rev Plant Biol 62: 549-566
72. Ralston L, Kwon ST, Schoenbeck M, Ralston J, Schenk DJ, Coates RM, Chappell J (2001) Cloning, heterologous expression, and functional characterization of 5-epi-aristolochene-1,3-dihydroxylase from tobacco (Nicotiana tabacum). Arch Biochem Biophys 393: 222-235
73. Reiling KK, Yoshikuni Y, Martin VJJ, Newman J, Bohlmann J, Keasling JD (2004) Mono and diterpene production in Escherichia coli. Biotechnol Bioeng 87: 200-212
74. Ro DK, Arimura G, Lau SY, Piers E, Bohlmann J (2005) Loblolly pine abietadienol/abietadienal oxidase PtAO (CYP720B1) is a multifunctional, multisubstrate cytochrome P450 monooxygenase. Proc Natl Acad Sci USA 102: 8060-8065
75. Sallaud C, Giacalone C, Töpfer R, Goepfert S, Bakaher N, Rösti S, Tissier A (2012) Characterization of two genes for the biosynthesis of the lab-dane diterpene Z-abienol in tobacco (Nicotiana tabacum) glandular tri-chomes. Plant J 72: 1-17
76. Schalk M, Pastore L, Mirata MA, Khim S, Schouwey M, Deguerry F, Pineda V, Rocci L, Daviet L (2012) Toward a biosynthetic route to sclareol and amber odorants. J Am Chem Soc 134: 18900-18903
77. Schmelz EA, Kaplan F, Huffaker A, Dafoe NJ, Vaughan MM, Ni X, Rocca JR, Alborn HT, Teal PE (2011) Identity, regulation, and activity of in-ducible diterpenoid phytoalexins in maize. Proc Natl Acad Sci USA 108: 5455-5460
78. Seki H, Ohyama K, Sawai S, Mizutani M, Ohnishi T, Sudo H, Akashi T, Aoki T, Saito K, Muranaka T (2008) Licorice b-amyrin 11-oxidase, a cytochrome P450 with a key role in the biosynthesis of the triterpene sweetener glycyrrhizin. Proc Natl Acad Sci USA 105: 14204-14209
79. Seo S, Gomi K, Kaku H, Abe H, Seto H, Nakatsu S, Neya M, Kobayashi M, Nakaho K, Ichinose Y, et al (2012) Identification of natural diter-penes that inhibit bacterial wilt disease in tobacco, tomato and Arabi-dopsis. Plant Cell Physiol 53: 1432-1444
80. Stofer Vogel B, Wildung MR, Vogel G, Croteau R (1996) Abietadiene synthase from grand fir (Abies grandis): cDNA isolation, characterization, and bacterial expression of a bifunctional diterpene cyclase involved in resin acid biosynthesis. J Biol Chem 271: 23262-23268
81. Sun TP, Kamiya Y (1994) The Arabidopsis GA1 locus encodes the cyclase ent-kaurene synthetase A of gibberellin biosynthesis. Plant Cell 6: 1509-1518
82. Swaminathan S, Morrone D, Wang Q, Fulton DB, Peters RJ (2009) CYP76M7 is an ent-cassadiene C11a-hydroxylase defining a second multifunctional diterpenoid biosynthetic gene cluster in rice. Plant Cell 21: 3315-3325
83. Theoduloz C, Rodríguez JA, Pertino M, Schmeda-Hirschmann G (2009) Antiproliferative activity of the diterpenes jatrophone and jatropholone and their derivatives. Planta Med 75: 1520-1522
84. Voinnet O, Rivas S, Mestre P, Baulcombe D (2003) An enhanced transient expression system in plants based on suppression of gene silencing by the p19 protein of tomato bushy stunt virus. Plant J 33: 949-956
85. Walker K, Croteau R (2001) Taxol biosynthetic genes. Phytochemistry 58: 1-7
86. Wang E, Wagner GJ (2003) Elucidation of the functions of genes central to diterpene metabolism in tobacco trichomes using posttranscriptional gene silencing. Planta 216: 686-691
87. Wang Q, Hillwig ML, Peters RJ (2011) CYP99A3: functional identification of a diterpene oxidase from the momilactone biosynthetic gene cluster in rice. Plant J 65: 87-95
88. Wang Q, Hillwig ML, Okada K, Yamazaki K, Wu Y, Swaminathan S, Yamane H, Peters RJ (2012a) Characterization of CYP76M5-8 indicates metabolic plasticity within a plant biosynthetic gene cluster. J Biol Chem 287: 6159-6168
89. Wang Q, Hillwig ML, Wu Y, Peters RJ (2012b) CYP701A8: a rice ent-kaurene oxidase paralog diverted to more specialized diterpenoid metabolism. Plant Physiol 158: 1418-1425
90. Wilderman PR, Peters RJ (2007) A single residue switch converts abieta-diene synthase into a pimaradiene specific cyclase. J Am Chem Soc 129: 15736-15737
91. Wildung MR, Croteau R (1996) A cDNA clone for taxadiene synthase, the diterpene cyclase that catalyzes the committed step of taxol biosynthesis. J Biol Chem 271: 9201-9204
92. Wilson SA, Roberts SC (2012) Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules. Plant Biotechnol J 10: 249-268
93. Wu Y, Hillwig ML, Wang Q, Peters RJ (2011) Parsing a multifunctional biosynthetic gene cluster from rice: Biochemical characterization of CYP71Z6 & 7. FEBS Lett 585: 3446-3451
94. Wu Y, Zhou K, Toyomasu T, Sugawara C, Oku M, Abe S, Usui M, Mitsuhashi W, Chono M, Chandler PM, et al (2012) Functional characterization of wheat copalyl diphosphate synthases sheds light on the early evolution of labdane-related diterpenoid metabolism in the cereals. Phytochemistry 84: 40-46
95. Wüst M, Little DB, Schalk M, Croteau R (2001) Hydroxylation of limonene enantiomers and analogs by recombinant (-)-limonene 3- and 6-hydroxylases from mint (Mentha) species: evidence for catalysis within sterically constrained active sites. Arch Biochem Biophys 387: 125-136
96. Xu M, Wilderman PR, Morrone D, Xu J, Roy A, Margis-Pinheiro M, Upadhyaya NM, Coates RM, Peters RJ (2007a) Functional characterization of the rice kaurene synthase-like gene family. Phytochemistry 68: 312-326
97. Xu M, Wilderman PR, Peters RJ (2007b) Following evolution's lead to a single residue switch for diterpene synthase product outcome. Proc Natl Acad Sci USA 104: 7397-7401
98. Yamaguchi S, Sun Tp, Kawaide H, Kamiya Y (1998) The GA2 locus of Arabidopsis thaliana encodes ent-kaurene synthase of gibberellin biosynthesis. Plant Physiol 116: 1271-1278
99. Zabka M, Pavela R, Gabrielova-Slezakova L (2011) Promising antifungal effect of some Euro-Asiatic plants against dangerous pathogenic and toxinogenic fungi. J Sci Food Agric 91: 492-497
100. Zerbe P, Chiang A, Yuen M, Hamberger B, Hamberger B, Draper JA, Britton R, Bohlmann J (2012a) Bifunctional cis-abienol synthase from Abies balsamea discovered by transcriptome sequencing and its implications for diterpenoid fragrance production. J Biol Chem 287: 12121-12131
101. Zerbe P, Chiang A, Bohlmann J (2012b) Mutational analysis of white spruce (Picea glauca) ent-kaurene synthase (PgKS) reveals common and distinct mechanisms of conifer diterpene synthases of general and specialized metabolism. Phytochemistry 74: 30-39
102. Zerbe P, Bohlmann J (2013) Bioproducts, biofuels, and perfumes: Conifer terpene synthases and their potential for metabolic engineering. Recent Adv Phytochem (in press)
103. Zhou K, Peters RJ (2011) Electrostatic effects on (di)terpene synthase product outcome. Chem Commun (Camb) 47: 4074-4080
104. Zhou K, Xu M, Tiernan M, Xie Q, Toyomasu T, Sugawara C, Oku M, Usui M, Mitsuhashi W, Chono M, et al (2012a) Functional characterization of wheat ent-kaurene(-like) synthases indicates continuing evolution of labdane-related diterpenoid metabolism in the cereals. Phytochemistry 84: 47-55
105. Zhou YJ, Gao W, Rong Q, Jin G, Chu H, Liu W, Yang W, Zhu Z, Li G, Zhu G, et al (2012b) Modular pathway engineering of diterpenoid synthases and the mevalonic acid pathway for miltiradiene production. J Am Chem Soc 134: 3234-3241
106. Zulak KG, Bohlmann J (2010) Terpenoid biosynthesis and specialized vascular cells of conifer defense. J Integr Plant Biol 52: 86-97